摘要
树突状细胞(DC)是公认为最有效的诱导适应性免疫应答的专职抗原呈递细胞,在变应性鼻炎发病机制中起着关键作用。DC通过病原体识别受体感知病原微生物的剌激,并解码、整合和递呈这些刺激产生的信号到T细胞,引起免疫应答。本文将从DC亚群和功能、过敏原识别到介导T细胞免疫应答及针对靶点DC的免疫疗法做系统性综述,以便于充分利用DC生物学知识为临床防治变应性鼻炎提供重要参考。
Dendritic cells(DC) are recognized as the most effective professional antigen presenting cells to induce adaptive immune response and play a key role in the pathogenesis of allergic rhinitis. DCs sense microbial stimuli through pathogen-recognition receptors and decode, integrate, and present information derived from such stimuli to T cells, thus cause immune responses. In this paper, we will make a systematic review on DC subsets and their functions, allergen recognition, T cell immune response and targeting immunotherapy, in order to provide some references for clinical prevention and treatment of allergic rhinitis by making full use of DC biological knowledge.
引文
[1]Licari A,Castagnoli R,Bottino C,et al.Emerging drugs for the treatment of perennial allergic rhinitis[J].Expert Opin Emerg Drugs,2016,21(1):57-67.
[2]Schlitzer A,Mcgovern N,Ginhoux F.Dendritic cells and monocyte-derived cells:Two complementary and integrated functional systems[J].Semin Cell Dev Biol,2015,41:9-22.
[3]Zhang H,Gregorio JD,Iwahori T,et al.A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes[J].Proc Natl Acad Sci U S A,2017,114(8):1988-1993.
[4]Bratke K,Klein C,Kuepper M,et al.Differential development of plasmacytoid dendritic cells in Th1-and Th2-like cytokine milieus[J].Allergy,2011,66(3):386-395.
[5]Gupta MR,Deepthi K,Garofalo RP.Differential response of BDCA-1+and BDCA-3+myeloid dendritic cells to respiratory syncytial virus infection[J].Respir Res,2013,14(1):71-71.
[6]Collin M,Bigley V.Human dendritic cell subsets:an update[J].Immunology,2018,154(1):3-20.
[7]Kleinjan A.The crucial role of dendritic cells in rhinitis[J].Curr Opin Allergy Clin Immunol,2011,11(1):12-17.
[8]Lee H,Ruane D,Law K,et al.Phenotype and function of nasal dendritic cells[J].Mucosal Immunol,2015,8(5):1083-1098.
[9]Pilette C,Jacobson MR,Ratajczak C,et al.Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis[J].Allergy,2013,68(3):312-321.
[10]Ayers CM,Schlosser RJ,O'connell BP,et al.Increased presence of dendritic cells and dendritic cell chemokines in the sinus mucosa of chronic rhinosinusitis with nasal polyps and allergic fungal rhinosinusitis[J].Int Forum Allergy Rhinol,2011,1(4):296-302.
[11]Belz GT,Nutt SL.Transcriptional programming of the dendritic cell network[J].Nat Rev Immunol,2012,12(2):101-113.
[12]Chistiakov DA,Sobenin IA,Orekhov AN,et al.Myeloid dendritic cells:Development,functions,and role in atherosclerotic inflammation[J].Immunobiology,2015,220(6):833-844.
[13]Worbs T,Hammerschmidt SI,Forster R.Dendritic cell migration in health and disease[J].Nat Rev Immunol,2017,17(1):30-48.
[14]Froidure A,Shen C,Pilette C.Dendritic cells revisited in human allergic rhinitis andasthma[J].Allergy,2016,71(2):137-148.
[15]Baleeiro RB,Walden P.Immature human DCs efficiently translocate endocytosed antigens into the cytosol for proteasomal processing[J].Mol Immunol,2017,88:148-154.
[16]Parola C,Salogni L,Vaira X,et al.Selective activation of human dendritic cells by OM-85 through a NF-κB and MAPK dependent pathway[J].PLos One,2013,8(12):e82867.
[17]Aguilera-Montilla N,Chamorro S,Nieto C,et al.Aryl hydrocarbon receptor contributes to the MEK/ERK-dependent maintenance of the immature state of human dendritic cells[J].Blood,2013,121(15):108-117.
[18]Shi ZH,Jiang WH,Wang M,et al.Inhibition of JAK/STATpathway restrains TSLP-activated dendritic cells mediated inflammatory T helper type 2 cell response in allergic rhinitis[J].Mol Cell Biochem,2017,430(1/2):161-169.
[19]徐向东,杨华安,胡溯,等.过表达STAT3对小鼠未成熟树突状细胞分化的影响[J].免疫学杂志,2017,33(6):482-487.
[20]León B,Ballesteros-Tato A,Lund FE.Dendritic cells and B cells:unexpected partners in Th2 development[J].JImmunol,2014,193(4):1531-1537.
[21]Vaahtomeri K,Brown M,Hauschild R,et al.Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia[J].Cell Rep,2017,19(5):902-909.
[22]Shen C,Hupin C,Froidure A,et al.Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in patients with allergic rhinitis and asthma[J].Clin Exp Allergy,2014,44(6):831-841.
[23]Jenkins SJ,Peronawright G,Worsley AG,et al.Dendritic cell expression of OX40 ligand acts as a costimulatory,not polarizing,signal for optimal Th2 priming and memory induction in vivo[J].J Immunol,2013,17(6):3515-3523.
[24]Rudulier CD,Mckinstry KK,Alyassin GA,et al.The number of responding CD4 T cells and the dose of antigen conjointly determine the TH1/TH2 phenotype by modulating B7/CD28 interactions[J].J Immunol,2014,192(11):5140-5150.
[25]Kamachi F,Harada N,Usui Y,et al.OX40 ligand regulates splenic CD8-dendritic cell-induced Th2 responses in vivo[J].Biochem Biophys Res Commun,2014,444(2):235-240.
[26]Ito T,Liu YJ,Arima K.Cellular and molecular mechanisms of TSLP function in human allergic disorders-TSLPprograms the“Th2 code”in dendritic cells[J].Allergol Int,2012,61(1):35-43.
[27]Wei P,Hu GH,Kang HY,et al.An aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress the Th17 response in allergic rhinitis patients[J].Lab Invest,2014,94(5):528-535.
[28]Liu Y,Yu HJ,Wang N,et al.Clara cell 10-kDa protein inhibits T(H)17 responses through modulating dendritic cells in the setting of allergic rhinitis[J].J Allergy Clin Immunol,2013,131(2):387-394.
[29]Novak N,Allam JP.Mucosal dendritic cells in allergy and immunotherapy[J].Allergy,2011,66:22-24.
[30]Wang CM,Chuang JJ.Effect of mite allergen immunotherapy on the altered phenotype of dendritic cells in allergic asthmatic children[J].Ann Allergy Asthma Immunol,2013,110(2):107-112.
[31]Yu S,Han B,Liu S,et al.Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper typel(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis[J].Mol Immunol,2017,90:172-181.
[32]Castillo J,Dimov V.Investigational drugs for the treatment of allergic rhinitis[J].Expert Opin Investig Drugs,2014,23(6):823-836.
[33]Erpenbeck VJ,Salapatek AM,Patel P,et al.Efficacy and safety of 10 day treatment with the CRTh2 antagonist QAV680 evaluated in patients with allergic rhinitis in an environmental exposure chamber[J].Eur Respir J,2014,44:4075
[34]陈娜,张双,高春燕.CRTH2受体拮抗剂对支气管哮喘树突状细胞功能的影响[J].免疫学杂志,2017,33(1):63-67.
[35]Yang SH,Yu CL,Yang YH,et al.The immune-modulatory effects of a mixed herbal formula on dendritic cells and CD4(+)T lymphocytes in the treatment of dust mite allergy asthma and perennial allergic rhinitis[J].J Asthma,2016,53(4):446-451.
[36]Cao PP,Shi LL,Xu K,et al.Dendritic cells in inflammatory sinonasal diseases[J].Clin Exp Allergy,2016,46(7):894-906.
