白细胞介素35在器官移植免疫中的研究进展
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摘要
白细胞介素35(IL-35)是近年发现并命名的IL-12家族细胞因子,它可由调节性T(Treg)细胞和调节性B(Breg)细胞特异性产生,是Treg和Breg细胞介导的负向免疫调节作用所必需的细胞因子。研究表明IL-35在器官移植免疫中发挥重要作用,针对IL-35的临床研发药物及细胞药物治疗可为抗移植排斥反应甚至诱导移植免疫耐受提供新的靶点和研究方向。
Interleukin 35(IL-35) is a kind of cytokine which is recently found and belongs to the IL-12 family. IL-35 is a cytokine secreted by regulatory T cells(Treg) and regulatory B cells(Breg), and is necessary for the negative immunoregulation mediated by Treg and Breg cells. Studies have shown that IL-35 plays an important role in organ transplantation immunity. The clinical research development drugs and cell therapy drugs for IL-35 can provide new targets and research directions for anti-graft rejection and even induction of transplantation immunity tolerance.
Interleukin 35(IL-35) is a kind of cytokine which is recently found and belongs to the IL-12 family. IL-35 is a cytokine secreted by regulatory T cells(Treg) and regulatory B cells(Breg), and is necessary for the negative immunoregulation mediated by Treg and Breg cells. Studies have shown that IL-35 plays an important role in organ transplantation immunity. The clinical research development drugs and cell therapy drugs for IL-35 can provide new targets and research directions for anti-graft rejection and even induction of transplantation immunity tolerance.
引文
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[24]Guo H,Wang W,Zhao N,et al.Inhibiting cardiac allograft rejection with interleukin-35 therapy combined with decitabine treatment in mice[J].Transpl Immunol,2013,29(1/4):99-104.
[25]李宝柱,赵娜,何向辉,等.白细胞介素35抑制小鼠心脏移植排斥反应的研究[J].中华器官移植杂志,2017,38(1):34-38.
[26]Rogosheske J R,Fargen A D,De For T E,et al.Higher therapeutic Cs A levels early post transplantation reduce risk of acute GVHD and improves survival[J].Bone Marrow Transplant,2014,49(1):122-125.
[27]Chang J Y,Sehgal S N.Pharmacology of rapamycin:a new irnrnunosuppressive agent[J].Br J Rheumatol,1991,30:62-65.
[28]Coutant A,Rescan C,Gilot D,et al.PI3K-FRAP/m To R pathway is critical for hepatocyte proliferation whereas MEK/ERK supports both proliferation and survival[J].Hepatology,2002,36(5):1079-1088.
[29]Zhao N,Li H,Yan Y,et al.Mesenchymal stem cells overexpressing IL-35 effectively inhibit CD4+T cell function[J].Cell Immunol,2017,312:61-66.
[30]Guo H,Zhao N,Gao H,et al.Mesenchymal stem cells overexpressing interleukin-35 propagate immunosuppressive effects in mice[J].Scand J Immunol,2017,86(5):389-395.
[2]Niedbala W,Wei X Q,Cai B,et al.IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells[J].Eur J Immunol,2007,37(11):3021-3029.
[3]Sawant D V,Hamilton K,Vignali D A.Interleukin-35:Expanding Its Job Profile[J].J Interferon Cytokine Res,2015,35(7):499-512.
[4]Zhang J,Lin Y,Li C,et al.IL-35 Decelerates the inflammatory process by regulating inflammatory cytokine secretion and M1/M2 macrophage ratio in psoriasis[J].J Immunol,2016,197(6):2131-2144.
[5]Collison L W,Chaturvedi V,Henderson A L,et al.IL-35-mediated induction of a potent regulatory T cell population[J].Nat Immunol,2010,11(12):1093-1101.
[6]Chaturvedi V,Collison L W,Guy C S,et al.Cutting edge:human regulatory T cells require IL-35 to mediate suppression and infectious tolerance[J].J Immunol,2013,191(4):2018.
[7]K?ser T,Müllebner A,Hartl R T,et al.Porcine T-helper and regulatory T cells exhibit versatile m RNA expression capabilities for cytokines and co-stimulatory molecules[J].Cytokine,2012,60(2):400-409.
[8]Xiang X,Xie Q.IL-35:a potential therapeutic target for controlling hepatitis B virus infection[J].J Dig Dis,2015,16(1):1-6.
[9]Wang R X,Yu C R,Dambuza I M,et al.Interleukin-35induces regulatory B cells that suppress autoimmune disease[J].Nat Med,2014,20(6):633-641.
[10]Shen P,Roch T,Lampropoulou V,et al.IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases[J].Nature,2014,507(7492):366-370.
[11]Collison L W,Pillai M R,Chaturvedi V,et al.Regulatory T cell suppression is potentiated by target T cells in a cell contact,IL-35-and IL-10-dependent manner[J].J Immunol,2009,182(10):6121-6128.
[12]Bettini M,Castellaw A H,Lennon G P,et al.Prevention of autoimmune diabetes by ectopic pancreatic-cell expression of interleukin-35[J].Diabetes,2012,61(6):1519-1526.
[13]Beatty P G,Hansen J A,Longton G M,et al.Marrow transplantation from HLA-matched unrelated donors for treatment of hematologic malignancies[J].Transplantation,1991,51(2):443-447.
[14]Shlomchik W D.Graft-versus-host disease[J].Nat Rev Immunol,2007,7(5):340-352.
[15]Zhang X,Zhou Y,Xu L,et al.Reduced IL-35 levels are associated with increased platelet aggregation and activation in patients with acute graft-versus-host disease after allogeneic hemotapoietic stem cell transplantation[J].Ann Hematol,2015,94(5):837-845.
[16]Liu Y,Wu Y,Wang Y,et al.IL-35 mitigates murine acute graft-versus-host disease with retention of graft-versusleukemia effects[J].Leukemia,2015,29(4):939-946.
[17]Taylor P A,Lees C J,Blazar B R.The infusion of ex vivo activated and expanded CD4+CD25+immune regulatory cells inhibits graft-versus-host disease lethality[J].Blood,2002,99(10):3493-3499.
[18]Weston L E,Geczy A F,Briscoe H.Production of IL-10by alloreactive sibling donor cells and its influence on the development of acute GVHD[J].Bone Marrow Transplant,2006,37(2):207-212.
[19]Tang Q,Bluestone J A.Regulatory T-cell therapy in transplantation:moving to the clinic[J].Cold Spring Harb Perspect Med,2013,3(11):a015552.
[20]Martinez-Llordella M,Puig-Pey I,Orlando G,et al.Multiparameter immune profiling of operational tolerance in liver transplantation[J].Am J Transplant,2007,7(2):309-319.
[21]Dijke I E,Korevaar S S,Caliskan K,et al.Inadequate immune regulatory function of CD4+CD25+bright+Foxp3+T cells in heart transplant patients who experience acute cellular rejection[J].Transplantation,2009,87(8):1191-1200.
[22]Hou C,Wu Q,Ouyang C,et al.Effects of an intravitreal injection of interleukin-35-expressing plasmid on proinflammatory and anti-inflammatory cytokines[J].Int J Mol Med,2016,38(3):713-720.
[23]Zongyi Y,Funian Z,Hao L,et al.Interleukin-35 mitigates the function of murine transplanted islet cells via regulation of Treg/Th17 ratio[J].PLo S One,2017,12(12):e0189617.
[24]Guo H,Wang W,Zhao N,et al.Inhibiting cardiac allograft rejection with interleukin-35 therapy combined with decitabine treatment in mice[J].Transpl Immunol,2013,29(1/4):99-104.
[25]李宝柱,赵娜,何向辉,等.白细胞介素35抑制小鼠心脏移植排斥反应的研究[J].中华器官移植杂志,2017,38(1):34-38.
[26]Rogosheske J R,Fargen A D,De For T E,et al.Higher therapeutic Cs A levels early post transplantation reduce risk of acute GVHD and improves survival[J].Bone Marrow Transplant,2014,49(1):122-125.
[27]Chang J Y,Sehgal S N.Pharmacology of rapamycin:a new irnrnunosuppressive agent[J].Br J Rheumatol,1991,30:62-65.
[28]Coutant A,Rescan C,Gilot D,et al.PI3K-FRAP/m To R pathway is critical for hepatocyte proliferation whereas MEK/ERK supports both proliferation and survival[J].Hepatology,2002,36(5):1079-1088.
[29]Zhao N,Li H,Yan Y,et al.Mesenchymal stem cells overexpressing IL-35 effectively inhibit CD4+T cell function[J].Cell Immunol,2017,312:61-66.
[30]Guo H,Zhao N,Gao H,et al.Mesenchymal stem cells overexpressing interleukin-35 propagate immunosuppressive effects in mice[J].Scand J Immunol,2017,86(5):389-395.