Crucial roles of macrophages in the pathogenesis of autoimmune disease
|
摘要
Macrophages are key players in various immune responses. In addition to functions in innate immunity such as antigen phagocytosis and cytokine production, antigen presentation by macrophage represents a link between innate and acquired immunity. During inflammatory processes, na?ve monocytes differentiate into proinflammatory M1 and anti-inflammatory M2 macrophages. Resident monocytes/macrophages contribute to immune response that maintains tissue-specific homeostasis. In the target organs of autoimmune diseases, macrophages have dual functions in both the induction and suppression of autoimmune responses, which are mediated by production of various cytokines and chemokines, or by interaction with other immune cells. This review focuses on selected autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sj?gren's syndrome, to illustrate the key roles of macrophages in the cellular or molecular pathogenesis of autoimmunity. In addition, the contribution of macrophages to each autoimmune disease is compared.
Macrophages are key players in various immune responses. In addition to functions in innate immunity such as antigen phagocytosis and cytokine production, antigen presentation by macrophage represents a link between innate and acquired immunity. During inflammatory processes, na?ve monocytes differentiate into proinflammatory M1 and anti-inflammatory M2 macrophages. Resident monocytes/macrophages contribute to immune response that maintains tissue-specific homeostasis. In the target organs of autoimmune diseases, macrophages have dual functions in both the induction and suppression of autoimmune responses, which are mediated by production of various cytokines and chemokines, or by interaction with other immune cells. This review focuses on selected autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sj?gren's syndrome, to illustrate the key roles of macrophages in the cellular or molecular pathogenesis of autoimmunity. In addition, the contribution of macrophages to each autoimmune disease is compared.
Macrophages are key players in various immune responses. In addition to functions in innate immunity such as antigen phagocytosis and cytokine production, antigen presentation by macrophage represents a link between innate and acquired immunity. During inflammatory processes, na?ve monocytes differentiate into proinflammatory M1 and anti-inflammatory M2 macrophages. Resident monocytes/macrophages contribute to immune response that maintains tissue-specific homeostasis. In the target organs of autoimmune diseases, macrophages have dual functions in both the induction and suppression of autoimmune responses, which are mediated by production of various cytokines and chemokines, or by interaction with other immune cells. This review focuses on selected autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, and Sj?gren's syndrome, to illustrate the key roles of macrophages in the cellular or molecular pathogenesis of autoimmunity. In addition, the contribution of macrophages to each autoimmune disease is compared.
引文
1 Cho JH,Feldman M.Heterogeneity of autoimmune diseases:pathophysiologic insights from genetics and implications for new therapies.Nat Med 2015;21:730-738[PMID:26121193 DOI:10.1038/nm.3897]
2 Mueller DL.Mechanisms maintaining peripheral tolerance.Nat Immunol 2010;11:21-27[PMID:20016506 DOI:10.1038/ni.1817]
3 Waldmann H.Tolerance:an overview and perspectives.Nat Rev Nephrol 2010;6:569-576[PMID:20717099 DOI:10.1038/nrneph.2010.108]
4 Liston A,Gray DH.Homeostatic control of regulatory T cell diversity.Nat Rev Immunol 2014;14:154-165[PMID:24481337DOI:10.1038/nri3605]
5 Hogquist KA,Jameson SC.The self-obsession of T cells:how TCR signaling thresholds affect fate‘decisions’and effector function.Nat Immunol 2014;15:815-823[PMID:25137456 DOI:10.1038/ni.2938]
6 Arango Duque G,Descoteaux A.Macrophage cytokines:involvement in immunity and infectious diseases.Front Immunol2014;5:491[PMID:25339958 DOI:10.3389/fimmu.2014.00491]
7 Wynn TA,Chawla A,Pollard JW.Macrophage biology in development,homeostasis and disease.Nature 2013;496:445-455[PMID:23619691 DOI:10.1038/nature12034]
8 Shi C,Pamer EG.Monocyte recruitment during infection and inflammation.Nat Rev Immunol 2011;11:762-774[PMID:21984070 DOI:10.1038/nri3070]
9 Murray PJ,Wynn TA.Protective and pathogenic functions of macrophage subsets.Nat Rev Immunol 2011;11:723-737[PMID:21997792 DOI:10.1038/nri3073]
10 Biswas SK,Mantovani A.Macrophage plasticity and interaction with lymphocyte subsets:cancer as a paradigm.Nat Immunol2010;11:889-896[PMID:20856220 DOI:10.1038/ni.1937]
11 Hotamisligil GS,Shargill NS,Spiegelman BM.Adipose ex-pression of tumor necrosis factor-alpha:direct role in obesity-linked insulin resistance.Science 1993;259:87-91[PMID:7678183 DOI:10.1126/science.7678183]
12 Chawla A,Nguyen KD,Goh YP.Macrophage-mediated inflam-mation in metabolic disease.Nat Rev Immunol 2011;11:738-749[PMID:21984069 DOI:10.1038/nri3071]
13 Tabas I,Bornfeldt KE.Macrophage Phenotype and Function in Different Stages of Atherosclerosis.Circ Res 2016;118:653-667[PMID:26892964 DOI:10.1161/CIRCRESAHA.115.306256]
14 Boyle JJ,Harrington HA,Piper E,Elderfield K,Stark J,Landis RC,Haskard DO.Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype.Am J Pathol 2009;174:1097-1108[PMID:19234137 DOI:10.2353/ajpath.2009.080431]
15 Colin S,Chinetti-Gbaguidi G,Staels B.Macrophage phenotypes in atherosclerosis.Immunol Rev 2014;262:153-166[PMID:25319333 DOI:10.1111/imr.12218]
16 Kadl A,Meher AK,Sharma PR,Lee MY,Doran AC,Johnstone SRElliott MR,Gruber F,Han J,Chen W,Kensler T,Ravichandran KSIsakson BE,Wamhoff BR,Leitinger N.Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2.Circ Res 2010;107:737-746[PMID:20651288 DOI:10.1161/CIRCRESAHA.109.215715]
17 Chinetti-Gbaguidi G,Colin S,Staels B.Macrophage subsets in atherosclerosis.Nat Rev Cardiol 2015;12:10-17[PMID:25367649DOI:10.1038/nrcardio.2014.173]
18 Erbel C,Akhavanpoor M,Okuyucu D,Wangler S,Dietz A,Zhao L,Stellos K,Little KM,Lasitschka F,Doesch A,Hakimi M,Dengler TJ,Giese T,Blessing E,Katus HA,Gleissner CA.IL-17Ainfluences essential functions of the monocyte/macrophage lineage and is involved in advanced murine and human atherosclerosis.JImmunol 2014;193:4344-4355[PMID:25261478 DOI:10.4049/jimmunol.1400181]
19 Mantovani A,Allavena P,Sica A,Balkwill F.Cancer-related inflammation.Nature 2008;454:436-444[PMID:18650914 DOI:10.1038/nature07205]
20 Qian BZ,Pollard JW.Macrophage diversity enhances tumor pro-gression and metastasis.Cell 2010;141:39-51[PMID:20371344DOI:10.1016/j.cell.2010.03.014]
21 Lewis CE,Pollard JW.Distinct role of macrophages in different tumor microenvironments.Cancer Res 2006;66:605-612[PMID:16423985 DOI:10.1158/0008-5472.CAN-05-4005]
22 Pollard JW.Tumour-educated macrophages promote tumour progression and metastasis.Nat Rev Cancer 2004;4:71-78[PMID:14708027 DOI:10.1038/nrc1256]
23 Nagata S,Hanayama R,Kawane K.Autoimmunity and the clearance of dead cells.Cell 2010;140:619-630[PMID:20211132DOI:10.1016/j.cell.2010.02.014]
24 Kawane K,Fukuyama H,Kondoh G,Takeda J,Ohsawa Y,Uchiyama Y,Nagata S.Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver.Science 2001;292:1546-1549[PMID:11375492 DOI:10.1126/science.292.5521.1546]
25 Kawane K,Ohtani M,Miwa K,Kizawa T,Kanbara Y,Yoshioka Y,Yoshikawa H,Nagata S.Chronic polyarthritis caused by mam-malian DNA that escapes from degradation in macrophages.Nature2006;443:998-1002[PMID:17066036 DOI:10.1038/nature05245]
26 Hanayama R,Tanaka M,Miyasaka K,Aozasa K,Koike MUchiyama Y,Nagata S.Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice.Science 2004;304:1147-1150[PMID:15155946 DOI:10.1126/science.1094359]
27 Fadok VA,Voelker DR,Campbell PA,Cohen JJ,Bratton DLHenson PM.Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.J Immunol 1992;148:2207-2216[PMID:1545126]
28 Hickey WF.The pathology of multiple sclerosis:a historical perspective.J Neuroimmunol 1999;98:37-44[PMID:10426360DOI:10.1016/S0165-5728(99)00079-X]
29 Banwell B,Bar-Or A,Arnold DL,Sadovnick D,Narayanan SMc Gowan M,O’Mahony J,Magalhaes S,Hanwell H,Vieth RTellier R,Vincent T,Disanto G,Ebers G,Wambera K,Connolly MB,Yager J,Mah JK,Booth F,Sebire G,Callen D,Meaney BDilenge ME,Lortie A,Pohl D,Doja A,Venketaswaran S,Levin SMacdonald EA,Meek D,Wood E,Lowry N,Buckley D,Yim CAwuku M,Cooper P,Grand’maison F,Baird JB,Bhan V,Marrie RA.Clinical,environmental,and genetic determinants of multiple sclerosis in children with acute demyelination:a prospective national cohort study.Lancet Neurol 2011;10:436-445[PMID:21459044 DOI:10.1016/S1474-4422(11)70045-X]
30 Almolda B,Gonzalez B,Castellano B.Antigen presentation in EAE:role of microglia,macrophages and dendritic cells.Front Biosci(Landmark Ed)2011;16:1157-1171[PMID:21196224DOI:10.2741/3781]
31 Jiang Z,Li H,Fitzgerald DC,Zhang GX,Rostami A.MOG(35-55)i.v suppresses experimental autoimmune encephalomyelitis partially through modulation of Th17 and JAK/STAT pathways Eur J Immunol 2009;39:789-799[PMID:19224632 DOI:10.1002/eji.200838427]
32 Rawji KS,Yong VW.The benefits and detriments of macrophages/microglia in models of multiple sclerosis.Clin Dev Immunol 2013;2013:948976[PMID:23840244 DOI:10.1155/2013/948976]
33 Abourbeh G,ThézéB,Maroy R,Dubois A,Brulon V,Fontyn YDolléF,Tavitian B,Boisgard R.Imaging microglial/macrophage activation in spinal cords of experimental autoimmune ence-phalomyelitis rats by positron emission tomography using the mit-ochondrial 18 k Da translocator protein radioligand[18F]DPA-714J Neurosci 2012;32:5728-5736[PMID:22539835 DOI:10.1523/JNEUROSCI.2900-11.2012]
34 Aguzzi A,Barres BA,Bennett ML.Microglia:scapegoat,saboteur or something else?Science 2013;339:156-161[PMID:23307732DOI:10.1126/science.1227901]
35 Ousman SS,Kubes P.Immune surveillance in the central nervous system.Nat Neurosci 2012;15:1096-1101[PMID:22837040 DOI:10.1038/nn.3161]
36 Dogan RN,Long N,Forde E,Dennis K,Kohm AP,Miller SDKarpus WJ.CCL22 regulates experimental autoimmune encepha-lomyelitis by controlling inflammatory macrophage accumulation and effector function.J Leukoc Biol 2011;89:93-104[PMID:20940325 DOI:10.1189/jlb.0810442]
37 Saederup N,Cardona AE,Croft K,Mizutani M,Cotleur AC,Tsou CL,Ransohoff RM,Charo IF.Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice.PLo S One 2010;5:e13693[PMID:21060874 DOI:10.1371/journal.pone.0013693]
38 Jiang Z,Jiang JX,Zhang GX.Macrophages:a double-edged sword in experimental autoimmune encephalomyelitis.Immunol Lett 2014;160:17-22[PMID:24698730 DOI:10.1016/j.imlet.2014.03.006]
39 Forde EA,Dogan RN,Karpus WJ.CCR4 contributes to the pathogenesis of experimental autoimmune encephalomyelitis by regulating inflammatory macrophage function.J Neuroimmunol2011;236:17-26[PMID:21575994 DOI:10.1016/j.jneuroim2011.04.008]
40 Columba-Cabezas S,Serafini B,Ambrosini E,Sanchez MPenna G,Adorini L,Aloisi F.Induction of macrophage-derived chemokine/CCL22 expression in experimental autoimmune encephalomyelitis and cultured microglia:implications for disease regulation.J Neuroimmunol 2002;130:10-21[PMID:12225884DOI:10.1016/S0165-5728(02)00170-4]
41 Jiang HR,Milovanovi?M,Allan D,Niedbala W,Besnard AG,Fukada SY,Alves-Filho JC,Togbe D,Goodyear CS,Linington C,Xu D,Lukic ML,Liew FY.IL-33 attenuates EAE by suppressing IL-17 and IFN-γproduction and inducing alternatively activated macrophages.Eur J Immunol 2012;42:1804-1814[PMID:22585447 DOI:10.1002/eji.201141947]
42 Pyonteck SM,Akkari L,Schuhmacher AJ,Bowman RL,Sevenich L,Quail DF,Olson OC,Quick ML,Huse JT,Teijeiro V,Setty M,Leslie CS,Oei Y,Pedraza A,Zhang J,Brennan CW,Sutton JC,Holland EC,Daniel D,Joyce JA.CSF-1R inhibition alters macrophage polarization and blocks glioma progression.Nat Med2013;19:1264-1272[PMID:24056773 DOI:10.1038/nm.3337]
43 Porcheray F,Viaud S,Rimaniol AC,Léone C,Samah B,Dereuddre-Bosquet N,Dormont D,Gras G.Macrophage activation switching:an asset for the resolution of inflammation.Clin Exp Immunol 2005;142:481-489[PMID:16297160 DOI:10.1111/j.1365-2249.2005.02934.x]
44 Denney L,Kok WL,Cole SL,Sanderson S,Mc Michael AJ,Ho LP.Activation of invariant NKT cells in early phase of experimental autoimmune encephalomyelitis results in differentiation of Ly6Chi inflammatory monocyte to M2 macrophages and improved outcome.J Immunol 2012;189:551-557[PMID:22685310 DOI:10.4049/jimmunol.1103608]
45 Liu C,Li Y,Yu J,Feng L,Hou S,Liu Y,Guo M,Xie Y,Meng J,Zhang H,Xiao B,Ma C.Targeting the shift from M1 to M2macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil.PLo S One 2013;8:e54841[PMID:23418431DOI:10.1371/journal.pone.0054841]
46 Klareskog L,Padyukov L,R?nnelid J,Alfredsson L.Genes,environment and immunity in the development of rheumatoid arthritis.Curr Opin Immunol 2006;18:650-655[PMID:17010589DOI:10.1016/j.coi.2006.06.004]
47 Mc Innes IB,Schett G.Cytokines in the pathogenesis of rheumatoid arthritis.Nat Rev Immunol 2007;7:429-442[PMID:17525752 DOI:10.1038/nri2094]
48 Mc Innes IB,Schett G.The pathogenesis of rheumatoid arthritis.N Engl J Med 2011;365:2205-2219[PMID:22150039 DOI:10.1056/NEJMra1004965]
49 Kennedy A,Fearon U,Veale DJ,Godson C.Macrophages in synovial inflammation.Front Immunol 2011;2:52[PMID:22566842 DOI:10.3389/fimmu.2011.00052]
50 Afzali B,Mitchell P,Lechler RI,John S,Lombardi G.Translational mini-review series on Th17 cells:induction of interleukin-17production by regulatory T cells.Clin Exp Immunol 2010;159:120-130[PMID:19912251 DOI:10.1111/j.1365-2249.2009.04038.x]
51 Erwig LP,Kluth DC,Walsh GM,Rees AJ.Initial cytokine exposure determines function of macrophages and renders them unresponsive to other cytokines.J Immunol 1998;161:1983-1988[PMID:9712070]
52 Wallet MA,Wallet SM,Guiulfo G,Sleasman JW,Goodenow MM.IFNgamma primes macrophages for inflammatory activation by high molecular weight hyaluronan.Cell Immunol 2010;262:84-88[PMID:20299009 DOI:10.1016/j.cellimm.2010.02.013]
53 Krausgruber T,Blazek K,Smallie T,Alzabin S,Lockstone H,Sahgal N,Hussell T,Feldmann M,Udalova IA.IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses.Nat Immunol 2011;12:231-238[PMID:21240265 DOI:10.1038/ni.1990]
54 Mantovani A,Sica A,Sozzani S,Allavena P,Vecchi A,Locati M.The chemokine system in diverse forms of macrophage activation and polarization.Trends Immunol 2004;25:677-686[PMID:15530839 DOI:10.1016/j.it.2004.09.015]
55 Biswas SK,Gangi L,Paul S,Schioppa T,Saccani A,Sironi M,Bottazzi B,Doni A,Vincenzo B,Pasqualini F,Vago L,Nebuloni M,Mantovani A,Sica A.A distinct and unique transcriptional program expressed by tumor-associated macrophages(defective NF-kappa B and enhanced IRF-3/STAT1 activation).Blood 2006;107:2112-2122[PMID:16269622 DOI:10.1182/blood-2005-01-0428]
56 Satoh T,Takeuchi O,Vandenbon A,Yasuda K,Tanaka YKumagai Y,Miyake T,Matsushita K,Okazaki T,Saitoh T,Honma K,Matsuyama T,Yui K,Tsujimura T,Standley DM,Nakanishi KNakai K,Akira S.The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.Nat Immunol 2010;11:936-944[PMID:20729857 DOI:10.1038/ni.1920]
57 Porta C,Rimoldi M,Raes G,Brys L,Ghezzi P,Di Liberto DDieli F,Ghisletti S,Natoli G,De Baetselier P,Mantovani A,Sica ATolerance and M2(alternative)macrophage polarization are related processes orchestrated by p50 nuclear factor kappa B.Proc Natl Acad Sci USA 2009;106:14978-14983[PMID:19706447 DOI:10.1073/pnas.0809784106]
58 Evans HG,Roostalu U,Walter GJ,Gullick NJ,Frederiksen KS,Roberts CA,Sumner J,Baeten DL,Gerwien JG,Cope APGeissmann F,Kirkham BW,Taams LS.TNF-αblockade induces IL-10 expression in human CD4+T cells.Nat Commun 2014;5:3199[PMID:24492460 DOI:10.1038/ncomms4199]
59 Boks MA,Kager-Groenland JR,Mousset CM,van Ham SMten Brinke A.Inhibition of TNF receptor signaling by anti-TNFαbiologicals primes na?ve CD4(+)T cells towards IL-10(+)T cells with a regulatory phenotype and function.Clin Immunol 2014;151:136-145[PMID:24568737 DOI:10.1016/j.clim.2014.02.008]
60 Ehrenstein MR,Evans JG,Singh A,Moore S,Warnes G,Isenberg DA,Mauri C.Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy.JExp Med 2004;200:277-285[PMID:15280421 DOI:10.1084/jem.20040165]
61 Valencia X,Stephens G,Goldbach-Mansky R,Wilson M,Shevach EM,Lipsky PE.TNF downmodulates the function of human CD4+CD25hi T-regulatory cells.Blood 2006;108:253-261[PMID:16537805 DOI:10.1182/blood-2005-11-4567]
62 Meusch U,Krasselt M,Rossol M,Baerwald C,Klingner MWagner U.In vitro response pattern of monocytes after tm TNFreverse signaling predicts response to anti-TNF therapy in rheumatoid arthritis.J Transl Med 2015;13:256[PMID:26251236DOI:10.1186/s12967-015-0620-z]
63 Smolen JS,Han C,Bala M,Maini RN,Kalden JR,van der Heijde D,Breedveld FC,Furst DE,Lipsky PE.Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement:a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study.Arthritis Rheum 2005;52:1020-1030[PMID:15818697 DOI:10.1002/art.20982]
64 Samson M,Audia S,Janikashvili N,Ciudad M,Trad M,Fraszczak J,Ornetti P,Maillefert JF,Miossec P,Bonnotte B.Brief report:inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis.Arthritis Rheum2012;64:2499-2503[PMID:22488116 DOI:10.1002/art.34477]
65 Pesce B,Soto L,Sabugo F,Wurmann P,Cuchacovich M,López MN,Sotelo PH,Molina MC,Aguillón JC,Catalán D.Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients Clin Exp Immunol 2013;171:237-242[PMID:23379428 DOI:10.1111/cei.12017]
66 Thiolat A,Semerano L,Pers YM,Biton J,Lemeiter D,Portales P,Quentin J,Jorgensen C,Decker P,Boissier MC,Louis-Plence P,Bessis N.Interleukin-6 receptor blockade enhances CD39+regulatory T cell development in rheumatoid arthritis and in experimental arthritis.Arthritis Rheumatol 2014;66:273-283[PMID:24504799 DOI:10.1002/art.38246]
67 Kikuchi J,Hashizume M,Kaneko Y,Yoshimoto K,Nishina N,Takeuchi T.Peripheral blood CD4(+)CD25(+)CD127(low)regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis:increase in regulatory T cells correlates with clinical response.Arthritis Res Ther 2015;17:10[PMID:25604867 DOI:10.1186/s13075-015-0526-4]
68 Sarantopoulos A,Tselios K,Gkougkourelas I,Pantoura M,Georgiadou AM,Boura P.Tocilizumab treatment leads to a rapid and sustained increase in Treg cell levels in rheumatoid arthritis patients:comment on the article by Thiolat et al.Arthritis Rheumatol 2014;66:2638[PMID:24891239 DOI:10.1002/art.38714]
69 Tono T,Aihara S,Hoshiyama T,Arinuma Y,Nagai T,Hirohata SEffects of anti-IL-6 receptor antibody on human monocytes.Mod Rheumatol 2015;25:79-84[PMID:24842475 DOI:10.3109/14397595.2014.914016]
70 Bozec A,Zaiss MM,Kagwiria R,Voll R,Rauh M,Chen Z,Mueller-Schmucker S,Kroczek RA,Heinzerling L,Moser M,Mellor AL,David JP,Schett G.T cell costimulation molecules CD80/86 inhibit osteoclast differentiation by inducing the IDO/tryptophan pathway.Sci Transl Med 2014;6:235ra60[PMID:24807557 DOI:10.1126/scitranslmed.3007764]
71 Fox RI.Sj?gren’s syndrome.Lancet 2005;366:321-331[PMID:16039337 DOI:10.1016/S0140-6736(05)66990-5]
72 Fox RI,Robinson CA,Curd JG,Kozin F,Howell FV.Sj?gren’s syndrome.Proposed criteria for classification.Arthritis Rheum1986;29:577-585[PMID:3718551 DOI:10.1002/art.1780290501]
73 Katsifis GE,Moutsopoulos NM,Wahl SM.T lymphocytes in Sj?gren’s syndrome:contributors to and regulators of patho-physiology.Clin Rev Allergy Immunol 2007;32:252-264[PMID:17992592 DOI:10.1007/s12016-007-8011-8]
74 Greenwell-Wild T,Moutsopoulos NM,Gliozzi M,Kapsogeorgou E,Rangel Z,Munson PJ,Moutsopoulos HM,Wahl SM.Chitinases in the salivary glands and circulation of patients with Sj?gren’s syndrome:macrophage harbingers of disease severity.Arthritis Rheum 2011;63:3103-3115[PMID:21618203 DOI:10.1002/art.30465]
75 Mustafa W,Zhu J,Deng G,Diab A,Link H,Frithiof L,Klinge B.Augmented levels of macrophage and Th1 cell-related cytokine m RNA in submandibular glands of MRL/lpr mice with autoimmune sialoadenitis.Clin Exp Immunol 1998;112:389-396[PMID:9649206 DOI:10.1046/j.1365-2249.1998.00609.x]
76 Zhou D,Chen YT,Chen F,Gallup M,Vijmasi T,Bahrami AF,Noble LB,van Rooijen N,Mc Namara NA.Critical involvement of macrophage infiltration in the development of Sj?gren’s syndrome-associated dry eye.Am J Pathol 2012;181:753-760[PMID:22770665 DOI:10.1016/j.ajpath.2012.05.014]
77 Jones ME,Thorburn AW,Britt KL,Hewitt KN,Wreford NG,Proietto J,Oz OK,Leury BJ,Robertson KM,Yao S,Simpson ER.Aromatase-deficient(Ar KO)mice have a phenotype of increased adiposity.Proc Natl Acad Sci USA 2000;97:12735-12740[PMID:11070087 DOI:10.1073/pnas.97.23.12735]
78 Misso ML,Murata Y,Boon WC,Jones ME,Britt KL,Simpson ER.Cellular and molecular characterization of the adipose phenotype of the aromatase-deficient mouse.Endocrinology 2003;144:1474-1480[PMID:12639931 DOI:10.1210/en.2002-221123]
79 Shim GJ,Warner M,Kim HJ,Andersson S,Liu L,Ekman J,Imamov O,Jones ME,Simpson ER,Gustafsson JA.Aromatase-deficient mice spontaneously develop a lymphoproliferative autoimmune disease resembling Sjogren’s syndrome.Proc Natl Acad Sci USA 2004;101:12628-12633[PMID:15314222 DOI:10.1073/pnas.0405099101]
80 Iwasa A,Arakaki R,Honma N,Ushio A,Yamada A,Kondo TKurosawa E,Kujiraoka S,Tsunematsu T,Kudo Y,Tanaka E,Yoshimura N,Harada N,Hayashi Y,Ishimaru N.Aromatase controls Sj?gren syndrome-like lesions through monocyte chemo-tactic protein-1 in target organ and adipose tissue-associated macrophages.Am J Pathol 2015;185:151-161[PMID:25447050DOI:10.1016/j.ajpath.2014.09.006]
2 Mueller DL.Mechanisms maintaining peripheral tolerance.Nat Immunol 2010;11:21-27[PMID:20016506 DOI:10.1038/ni.1817]
3 Waldmann H.Tolerance:an overview and perspectives.Nat Rev Nephrol 2010;6:569-576[PMID:20717099 DOI:10.1038/nrneph.2010.108]
4 Liston A,Gray DH.Homeostatic control of regulatory T cell diversity.Nat Rev Immunol 2014;14:154-165[PMID:24481337DOI:10.1038/nri3605]
5 Hogquist KA,Jameson SC.The self-obsession of T cells:how TCR signaling thresholds affect fate‘decisions’and effector function.Nat Immunol 2014;15:815-823[PMID:25137456 DOI:10.1038/ni.2938]
6 Arango Duque G,Descoteaux A.Macrophage cytokines:involvement in immunity and infectious diseases.Front Immunol2014;5:491[PMID:25339958 DOI:10.3389/fimmu.2014.00491]
7 Wynn TA,Chawla A,Pollard JW.Macrophage biology in development,homeostasis and disease.Nature 2013;496:445-455[PMID:23619691 DOI:10.1038/nature12034]
8 Shi C,Pamer EG.Monocyte recruitment during infection and inflammation.Nat Rev Immunol 2011;11:762-774[PMID:21984070 DOI:10.1038/nri3070]
9 Murray PJ,Wynn TA.Protective and pathogenic functions of macrophage subsets.Nat Rev Immunol 2011;11:723-737[PMID:21997792 DOI:10.1038/nri3073]
10 Biswas SK,Mantovani A.Macrophage plasticity and interaction with lymphocyte subsets:cancer as a paradigm.Nat Immunol2010;11:889-896[PMID:20856220 DOI:10.1038/ni.1937]
11 Hotamisligil GS,Shargill NS,Spiegelman BM.Adipose ex-pression of tumor necrosis factor-alpha:direct role in obesity-linked insulin resistance.Science 1993;259:87-91[PMID:7678183 DOI:10.1126/science.7678183]
12 Chawla A,Nguyen KD,Goh YP.Macrophage-mediated inflam-mation in metabolic disease.Nat Rev Immunol 2011;11:738-749[PMID:21984069 DOI:10.1038/nri3071]
13 Tabas I,Bornfeldt KE.Macrophage Phenotype and Function in Different Stages of Atherosclerosis.Circ Res 2016;118:653-667[PMID:26892964 DOI:10.1161/CIRCRESAHA.115.306256]
14 Boyle JJ,Harrington HA,Piper E,Elderfield K,Stark J,Landis RC,Haskard DO.Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype.Am J Pathol 2009;174:1097-1108[PMID:19234137 DOI:10.2353/ajpath.2009.080431]
15 Colin S,Chinetti-Gbaguidi G,Staels B.Macrophage phenotypes in atherosclerosis.Immunol Rev 2014;262:153-166[PMID:25319333 DOI:10.1111/imr.12218]
16 Kadl A,Meher AK,Sharma PR,Lee MY,Doran AC,Johnstone SRElliott MR,Gruber F,Han J,Chen W,Kensler T,Ravichandran KSIsakson BE,Wamhoff BR,Leitinger N.Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2.Circ Res 2010;107:737-746[PMID:20651288 DOI:10.1161/CIRCRESAHA.109.215715]
17 Chinetti-Gbaguidi G,Colin S,Staels B.Macrophage subsets in atherosclerosis.Nat Rev Cardiol 2015;12:10-17[PMID:25367649DOI:10.1038/nrcardio.2014.173]
18 Erbel C,Akhavanpoor M,Okuyucu D,Wangler S,Dietz A,Zhao L,Stellos K,Little KM,Lasitschka F,Doesch A,Hakimi M,Dengler TJ,Giese T,Blessing E,Katus HA,Gleissner CA.IL-17Ainfluences essential functions of the monocyte/macrophage lineage and is involved in advanced murine and human atherosclerosis.JImmunol 2014;193:4344-4355[PMID:25261478 DOI:10.4049/jimmunol.1400181]
19 Mantovani A,Allavena P,Sica A,Balkwill F.Cancer-related inflammation.Nature 2008;454:436-444[PMID:18650914 DOI:10.1038/nature07205]
20 Qian BZ,Pollard JW.Macrophage diversity enhances tumor pro-gression and metastasis.Cell 2010;141:39-51[PMID:20371344DOI:10.1016/j.cell.2010.03.014]
21 Lewis CE,Pollard JW.Distinct role of macrophages in different tumor microenvironments.Cancer Res 2006;66:605-612[PMID:16423985 DOI:10.1158/0008-5472.CAN-05-4005]
22 Pollard JW.Tumour-educated macrophages promote tumour progression and metastasis.Nat Rev Cancer 2004;4:71-78[PMID:14708027 DOI:10.1038/nrc1256]
23 Nagata S,Hanayama R,Kawane K.Autoimmunity and the clearance of dead cells.Cell 2010;140:619-630[PMID:20211132DOI:10.1016/j.cell.2010.02.014]
24 Kawane K,Fukuyama H,Kondoh G,Takeda J,Ohsawa Y,Uchiyama Y,Nagata S.Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver.Science 2001;292:1546-1549[PMID:11375492 DOI:10.1126/science.292.5521.1546]
25 Kawane K,Ohtani M,Miwa K,Kizawa T,Kanbara Y,Yoshioka Y,Yoshikawa H,Nagata S.Chronic polyarthritis caused by mam-malian DNA that escapes from degradation in macrophages.Nature2006;443:998-1002[PMID:17066036 DOI:10.1038/nature05245]
26 Hanayama R,Tanaka M,Miyasaka K,Aozasa K,Koike MUchiyama Y,Nagata S.Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice.Science 2004;304:1147-1150[PMID:15155946 DOI:10.1126/science.1094359]
27 Fadok VA,Voelker DR,Campbell PA,Cohen JJ,Bratton DLHenson PM.Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.J Immunol 1992;148:2207-2216[PMID:1545126]
28 Hickey WF.The pathology of multiple sclerosis:a historical perspective.J Neuroimmunol 1999;98:37-44[PMID:10426360DOI:10.1016/S0165-5728(99)00079-X]
29 Banwell B,Bar-Or A,Arnold DL,Sadovnick D,Narayanan SMc Gowan M,O’Mahony J,Magalhaes S,Hanwell H,Vieth RTellier R,Vincent T,Disanto G,Ebers G,Wambera K,Connolly MB,Yager J,Mah JK,Booth F,Sebire G,Callen D,Meaney BDilenge ME,Lortie A,Pohl D,Doja A,Venketaswaran S,Levin SMacdonald EA,Meek D,Wood E,Lowry N,Buckley D,Yim CAwuku M,Cooper P,Grand’maison F,Baird JB,Bhan V,Marrie RA.Clinical,environmental,and genetic determinants of multiple sclerosis in children with acute demyelination:a prospective national cohort study.Lancet Neurol 2011;10:436-445[PMID:21459044 DOI:10.1016/S1474-4422(11)70045-X]
30 Almolda B,Gonzalez B,Castellano B.Antigen presentation in EAE:role of microglia,macrophages and dendritic cells.Front Biosci(Landmark Ed)2011;16:1157-1171[PMID:21196224DOI:10.2741/3781]
31 Jiang Z,Li H,Fitzgerald DC,Zhang GX,Rostami A.MOG(35-55)i.v suppresses experimental autoimmune encephalomyelitis partially through modulation of Th17 and JAK/STAT pathways Eur J Immunol 2009;39:789-799[PMID:19224632 DOI:10.1002/eji.200838427]
32 Rawji KS,Yong VW.The benefits and detriments of macrophages/microglia in models of multiple sclerosis.Clin Dev Immunol 2013;2013:948976[PMID:23840244 DOI:10.1155/2013/948976]
33 Abourbeh G,ThézéB,Maroy R,Dubois A,Brulon V,Fontyn YDolléF,Tavitian B,Boisgard R.Imaging microglial/macrophage activation in spinal cords of experimental autoimmune ence-phalomyelitis rats by positron emission tomography using the mit-ochondrial 18 k Da translocator protein radioligand[18F]DPA-714J Neurosci 2012;32:5728-5736[PMID:22539835 DOI:10.1523/JNEUROSCI.2900-11.2012]
34 Aguzzi A,Barres BA,Bennett ML.Microglia:scapegoat,saboteur or something else?Science 2013;339:156-161[PMID:23307732DOI:10.1126/science.1227901]
35 Ousman SS,Kubes P.Immune surveillance in the central nervous system.Nat Neurosci 2012;15:1096-1101[PMID:22837040 DOI:10.1038/nn.3161]
36 Dogan RN,Long N,Forde E,Dennis K,Kohm AP,Miller SDKarpus WJ.CCL22 regulates experimental autoimmune encepha-lomyelitis by controlling inflammatory macrophage accumulation and effector function.J Leukoc Biol 2011;89:93-104[PMID:20940325 DOI:10.1189/jlb.0810442]
37 Saederup N,Cardona AE,Croft K,Mizutani M,Cotleur AC,Tsou CL,Ransohoff RM,Charo IF.Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice.PLo S One 2010;5:e13693[PMID:21060874 DOI:10.1371/journal.pone.0013693]
38 Jiang Z,Jiang JX,Zhang GX.Macrophages:a double-edged sword in experimental autoimmune encephalomyelitis.Immunol Lett 2014;160:17-22[PMID:24698730 DOI:10.1016/j.imlet.2014.03.006]
39 Forde EA,Dogan RN,Karpus WJ.CCR4 contributes to the pathogenesis of experimental autoimmune encephalomyelitis by regulating inflammatory macrophage function.J Neuroimmunol2011;236:17-26[PMID:21575994 DOI:10.1016/j.jneuroim2011.04.008]
40 Columba-Cabezas S,Serafini B,Ambrosini E,Sanchez MPenna G,Adorini L,Aloisi F.Induction of macrophage-derived chemokine/CCL22 expression in experimental autoimmune encephalomyelitis and cultured microglia:implications for disease regulation.J Neuroimmunol 2002;130:10-21[PMID:12225884DOI:10.1016/S0165-5728(02)00170-4]
41 Jiang HR,Milovanovi?M,Allan D,Niedbala W,Besnard AG,Fukada SY,Alves-Filho JC,Togbe D,Goodyear CS,Linington C,Xu D,Lukic ML,Liew FY.IL-33 attenuates EAE by suppressing IL-17 and IFN-γproduction and inducing alternatively activated macrophages.Eur J Immunol 2012;42:1804-1814[PMID:22585447 DOI:10.1002/eji.201141947]
42 Pyonteck SM,Akkari L,Schuhmacher AJ,Bowman RL,Sevenich L,Quail DF,Olson OC,Quick ML,Huse JT,Teijeiro V,Setty M,Leslie CS,Oei Y,Pedraza A,Zhang J,Brennan CW,Sutton JC,Holland EC,Daniel D,Joyce JA.CSF-1R inhibition alters macrophage polarization and blocks glioma progression.Nat Med2013;19:1264-1272[PMID:24056773 DOI:10.1038/nm.3337]
43 Porcheray F,Viaud S,Rimaniol AC,Léone C,Samah B,Dereuddre-Bosquet N,Dormont D,Gras G.Macrophage activation switching:an asset for the resolution of inflammation.Clin Exp Immunol 2005;142:481-489[PMID:16297160 DOI:10.1111/j.1365-2249.2005.02934.x]
44 Denney L,Kok WL,Cole SL,Sanderson S,Mc Michael AJ,Ho LP.Activation of invariant NKT cells in early phase of experimental autoimmune encephalomyelitis results in differentiation of Ly6Chi inflammatory monocyte to M2 macrophages and improved outcome.J Immunol 2012;189:551-557[PMID:22685310 DOI:10.4049/jimmunol.1103608]
45 Liu C,Li Y,Yu J,Feng L,Hou S,Liu Y,Guo M,Xie Y,Meng J,Zhang H,Xiao B,Ma C.Targeting the shift from M1 to M2macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil.PLo S One 2013;8:e54841[PMID:23418431DOI:10.1371/journal.pone.0054841]
46 Klareskog L,Padyukov L,R?nnelid J,Alfredsson L.Genes,environment and immunity in the development of rheumatoid arthritis.Curr Opin Immunol 2006;18:650-655[PMID:17010589DOI:10.1016/j.coi.2006.06.004]
47 Mc Innes IB,Schett G.Cytokines in the pathogenesis of rheumatoid arthritis.Nat Rev Immunol 2007;7:429-442[PMID:17525752 DOI:10.1038/nri2094]
48 Mc Innes IB,Schett G.The pathogenesis of rheumatoid arthritis.N Engl J Med 2011;365:2205-2219[PMID:22150039 DOI:10.1056/NEJMra1004965]
49 Kennedy A,Fearon U,Veale DJ,Godson C.Macrophages in synovial inflammation.Front Immunol 2011;2:52[PMID:22566842 DOI:10.3389/fimmu.2011.00052]
50 Afzali B,Mitchell P,Lechler RI,John S,Lombardi G.Translational mini-review series on Th17 cells:induction of interleukin-17production by regulatory T cells.Clin Exp Immunol 2010;159:120-130[PMID:19912251 DOI:10.1111/j.1365-2249.2009.04038.x]
51 Erwig LP,Kluth DC,Walsh GM,Rees AJ.Initial cytokine exposure determines function of macrophages and renders them unresponsive to other cytokines.J Immunol 1998;161:1983-1988[PMID:9712070]
52 Wallet MA,Wallet SM,Guiulfo G,Sleasman JW,Goodenow MM.IFNgamma primes macrophages for inflammatory activation by high molecular weight hyaluronan.Cell Immunol 2010;262:84-88[PMID:20299009 DOI:10.1016/j.cellimm.2010.02.013]
53 Krausgruber T,Blazek K,Smallie T,Alzabin S,Lockstone H,Sahgal N,Hussell T,Feldmann M,Udalova IA.IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses.Nat Immunol 2011;12:231-238[PMID:21240265 DOI:10.1038/ni.1990]
54 Mantovani A,Sica A,Sozzani S,Allavena P,Vecchi A,Locati M.The chemokine system in diverse forms of macrophage activation and polarization.Trends Immunol 2004;25:677-686[PMID:15530839 DOI:10.1016/j.it.2004.09.015]
55 Biswas SK,Gangi L,Paul S,Schioppa T,Saccani A,Sironi M,Bottazzi B,Doni A,Vincenzo B,Pasqualini F,Vago L,Nebuloni M,Mantovani A,Sica A.A distinct and unique transcriptional program expressed by tumor-associated macrophages(defective NF-kappa B and enhanced IRF-3/STAT1 activation).Blood 2006;107:2112-2122[PMID:16269622 DOI:10.1182/blood-2005-01-0428]
56 Satoh T,Takeuchi O,Vandenbon A,Yasuda K,Tanaka YKumagai Y,Miyake T,Matsushita K,Okazaki T,Saitoh T,Honma K,Matsuyama T,Yui K,Tsujimura T,Standley DM,Nakanishi KNakai K,Akira S.The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.Nat Immunol 2010;11:936-944[PMID:20729857 DOI:10.1038/ni.1920]
57 Porta C,Rimoldi M,Raes G,Brys L,Ghezzi P,Di Liberto DDieli F,Ghisletti S,Natoli G,De Baetselier P,Mantovani A,Sica ATolerance and M2(alternative)macrophage polarization are related processes orchestrated by p50 nuclear factor kappa B.Proc Natl Acad Sci USA 2009;106:14978-14983[PMID:19706447 DOI:10.1073/pnas.0809784106]
58 Evans HG,Roostalu U,Walter GJ,Gullick NJ,Frederiksen KS,Roberts CA,Sumner J,Baeten DL,Gerwien JG,Cope APGeissmann F,Kirkham BW,Taams LS.TNF-αblockade induces IL-10 expression in human CD4+T cells.Nat Commun 2014;5:3199[PMID:24492460 DOI:10.1038/ncomms4199]
59 Boks MA,Kager-Groenland JR,Mousset CM,van Ham SMten Brinke A.Inhibition of TNF receptor signaling by anti-TNFαbiologicals primes na?ve CD4(+)T cells towards IL-10(+)T cells with a regulatory phenotype and function.Clin Immunol 2014;151:136-145[PMID:24568737 DOI:10.1016/j.clim.2014.02.008]
60 Ehrenstein MR,Evans JG,Singh A,Moore S,Warnes G,Isenberg DA,Mauri C.Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy.JExp Med 2004;200:277-285[PMID:15280421 DOI:10.1084/jem.20040165]
61 Valencia X,Stephens G,Goldbach-Mansky R,Wilson M,Shevach EM,Lipsky PE.TNF downmodulates the function of human CD4+CD25hi T-regulatory cells.Blood 2006;108:253-261[PMID:16537805 DOI:10.1182/blood-2005-11-4567]
62 Meusch U,Krasselt M,Rossol M,Baerwald C,Klingner MWagner U.In vitro response pattern of monocytes after tm TNFreverse signaling predicts response to anti-TNF therapy in rheumatoid arthritis.J Transl Med 2015;13:256[PMID:26251236DOI:10.1186/s12967-015-0620-z]
63 Smolen JS,Han C,Bala M,Maini RN,Kalden JR,van der Heijde D,Breedveld FC,Furst DE,Lipsky PE.Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement:a detailed subanalysis of data from the anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study.Arthritis Rheum 2005;52:1020-1030[PMID:15818697 DOI:10.1002/art.20982]
64 Samson M,Audia S,Janikashvili N,Ciudad M,Trad M,Fraszczak J,Ornetti P,Maillefert JF,Miossec P,Bonnotte B.Brief report:inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis.Arthritis Rheum2012;64:2499-2503[PMID:22488116 DOI:10.1002/art.34477]
65 Pesce B,Soto L,Sabugo F,Wurmann P,Cuchacovich M,López MN,Sotelo PH,Molina MC,Aguillón JC,Catalán D.Effect of interleukin-6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients Clin Exp Immunol 2013;171:237-242[PMID:23379428 DOI:10.1111/cei.12017]
66 Thiolat A,Semerano L,Pers YM,Biton J,Lemeiter D,Portales P,Quentin J,Jorgensen C,Decker P,Boissier MC,Louis-Plence P,Bessis N.Interleukin-6 receptor blockade enhances CD39+regulatory T cell development in rheumatoid arthritis and in experimental arthritis.Arthritis Rheumatol 2014;66:273-283[PMID:24504799 DOI:10.1002/art.38246]
67 Kikuchi J,Hashizume M,Kaneko Y,Yoshimoto K,Nishina N,Takeuchi T.Peripheral blood CD4(+)CD25(+)CD127(low)regulatory T cells are significantly increased by tocilizumab treatment in patients with rheumatoid arthritis:increase in regulatory T cells correlates with clinical response.Arthritis Res Ther 2015;17:10[PMID:25604867 DOI:10.1186/s13075-015-0526-4]
68 Sarantopoulos A,Tselios K,Gkougkourelas I,Pantoura M,Georgiadou AM,Boura P.Tocilizumab treatment leads to a rapid and sustained increase in Treg cell levels in rheumatoid arthritis patients:comment on the article by Thiolat et al.Arthritis Rheumatol 2014;66:2638[PMID:24891239 DOI:10.1002/art.38714]
69 Tono T,Aihara S,Hoshiyama T,Arinuma Y,Nagai T,Hirohata SEffects of anti-IL-6 receptor antibody on human monocytes.Mod Rheumatol 2015;25:79-84[PMID:24842475 DOI:10.3109/14397595.2014.914016]
70 Bozec A,Zaiss MM,Kagwiria R,Voll R,Rauh M,Chen Z,Mueller-Schmucker S,Kroczek RA,Heinzerling L,Moser M,Mellor AL,David JP,Schett G.T cell costimulation molecules CD80/86 inhibit osteoclast differentiation by inducing the IDO/tryptophan pathway.Sci Transl Med 2014;6:235ra60[PMID:24807557 DOI:10.1126/scitranslmed.3007764]
71 Fox RI.Sj?gren’s syndrome.Lancet 2005;366:321-331[PMID:16039337 DOI:10.1016/S0140-6736(05)66990-5]
72 Fox RI,Robinson CA,Curd JG,Kozin F,Howell FV.Sj?gren’s syndrome.Proposed criteria for classification.Arthritis Rheum1986;29:577-585[PMID:3718551 DOI:10.1002/art.1780290501]
73 Katsifis GE,Moutsopoulos NM,Wahl SM.T lymphocytes in Sj?gren’s syndrome:contributors to and regulators of patho-physiology.Clin Rev Allergy Immunol 2007;32:252-264[PMID:17992592 DOI:10.1007/s12016-007-8011-8]
74 Greenwell-Wild T,Moutsopoulos NM,Gliozzi M,Kapsogeorgou E,Rangel Z,Munson PJ,Moutsopoulos HM,Wahl SM.Chitinases in the salivary glands and circulation of patients with Sj?gren’s syndrome:macrophage harbingers of disease severity.Arthritis Rheum 2011;63:3103-3115[PMID:21618203 DOI:10.1002/art.30465]
75 Mustafa W,Zhu J,Deng G,Diab A,Link H,Frithiof L,Klinge B.Augmented levels of macrophage and Th1 cell-related cytokine m RNA in submandibular glands of MRL/lpr mice with autoimmune sialoadenitis.Clin Exp Immunol 1998;112:389-396[PMID:9649206 DOI:10.1046/j.1365-2249.1998.00609.x]
76 Zhou D,Chen YT,Chen F,Gallup M,Vijmasi T,Bahrami AF,Noble LB,van Rooijen N,Mc Namara NA.Critical involvement of macrophage infiltration in the development of Sj?gren’s syndrome-associated dry eye.Am J Pathol 2012;181:753-760[PMID:22770665 DOI:10.1016/j.ajpath.2012.05.014]
77 Jones ME,Thorburn AW,Britt KL,Hewitt KN,Wreford NG,Proietto J,Oz OK,Leury BJ,Robertson KM,Yao S,Simpson ER.Aromatase-deficient(Ar KO)mice have a phenotype of increased adiposity.Proc Natl Acad Sci USA 2000;97:12735-12740[PMID:11070087 DOI:10.1073/pnas.97.23.12735]
78 Misso ML,Murata Y,Boon WC,Jones ME,Britt KL,Simpson ER.Cellular and molecular characterization of the adipose phenotype of the aromatase-deficient mouse.Endocrinology 2003;144:1474-1480[PMID:12639931 DOI:10.1210/en.2002-221123]
79 Shim GJ,Warner M,Kim HJ,Andersson S,Liu L,Ekman J,Imamov O,Jones ME,Simpson ER,Gustafsson JA.Aromatase-deficient mice spontaneously develop a lymphoproliferative autoimmune disease resembling Sjogren’s syndrome.Proc Natl Acad Sci USA 2004;101:12628-12633[PMID:15314222 DOI:10.1073/pnas.0405099101]
80 Iwasa A,Arakaki R,Honma N,Ushio A,Yamada A,Kondo TKurosawa E,Kujiraoka S,Tsunematsu T,Kudo Y,Tanaka E,Yoshimura N,Harada N,Hayashi Y,Ishimaru N.Aromatase controls Sj?gren syndrome-like lesions through monocyte chemo-tactic protein-1 in target organ and adipose tissue-associated macrophages.Am J Pathol 2015;185:151-161[PMID:25447050DOI:10.1016/j.ajpath.2014.09.006]