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摘要: Ⅰ型自身免疫性胰腺炎(autoimmune pancreatitis，AIP)是一种以炎症和纤维化为主的胰腺炎，属于IgG4相关性疾病。目前关于Ⅰ型AIP的发病机制认识尚浅，普遍认为其发病是遗传、环境、免疫等多方面因素的综合结果。近年来，在Ⅰ型AIP发病的细胞和分子机制方面取得了诸多进展，本文主要从免疫学角度阐述其发病机制及研究进展。
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关键词:
- 自身免疫性胰腺炎 /
- IgG4相关性疾病 /
- 浆母细胞 /
- 滤泡辅助性T淋巴细胞 /
- 浆细胞样树突状细胞
Abstract: Type Ⅰ autoimmune pancreatitis (AIP) is a type of pancreatitis with a predominantly inflammatory and fibrotic nature and is an IgG4-related disease. The pathogenesis of type Ⅰ AIP is still poorly understood, but it is generally believed that it is the result of a combination of genetic, environmental, and immune factors. In recent years, many advances have been made in the cellular and molecular mechanisms of the pathogenesis of type Ⅰ AIP. Therefore, this article aims to review the research progress of the pathogenesis of this disease from the immunological perspective.作者贡献：刘屹霄和杨莹韵负责查阅文献、撰写及修订论文；杨爱明负责设计选题和审校论文。利益冲突：所有作者均声明不存在利益冲突 -
[1] Löhr JM, Vujasinovic M, Rosendahl J, et al. IgG4-related diseases of the digestive tract[J]. Nat Rev Gastroenterol Hepatol, 2022, 19: 185-97. doi: 10.1038/s41575-021-00529-y [2] Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology[J]. Pancreas, 2011, 40: 352-358. doi: 10.1097/MPA.0b013e3182142fd2 [3] Naitoh I, Kamisawa T, Tanaka A, et al. Clinical characteristics of immunoglobulin IgG4-related sclerosing chol-angitis: Comparison of cases with and without autoimmune pancreatitis in a large cohort[J]. Dig Liver Dis, 2021, 53: 1308-1314. doi: 10.1016/j.dld.2021.02.009 [4] Nishimori I, Tamakoshi A, Kawa S, et al. Influence of steroid therapy on the course of diabetes mellitus in patients with autoimmune pancreatitis: findings from a nationwide survey in Japan[J]. Pancreas, 2006, 32: 244-248. doi: 10.1097/01.mpa.0000202950.02988.07 [5] Kamisawa T, Egawa N, Inokuma S, et al. Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy[J]. Pancreas, 2003, 27: 235-238. [6] Javed AA, Wright MJ, Ding D, et al. Autoimmune Pancreatitis: A Critical Analysis of the Surgical Experience in an Era of Modern Diagnostics[J]. Pancreas, 2021, 50: 556-563. doi: 10.1097/MPA.0000000000001812 [7] Frulloni L, Scattolini C, Katsotourchi AM, et al. Exocrine and Endocrine Pancreatic Function in 21 Patients Suffering from Autoimmune Pancreatitis before and after Steroid Treatment[J]. Pancreatology, 2010, 10: 129-133. doi: 10.1159/000265945 [8] Estrada P, Pfau P. Diagnosing autoimmune pancreatitis: choosing your weapon[J]. Gastrointest Endosc, 2020, 91: 382-384. doi: 10.1016/j.gie.2019.11.037 [9] Arora K, Rivera M, Ting DT, et al. The histological diagnosis of IgG4-related disease on small biopsies: challenges and pitfalls[J]. Histopathology, 2019, 74: 688-698. doi: 10.1111/his.13787 [10] Okazaki K, Kawa S, Kamisawa T, et al. Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020[J]. J Gastroenterol, 2022, 57: 225-245. doi: 10.1007/s00535-022-01857-9 [11] 张盼盼, 张文. IgG4相关性自身免疫性胰腺炎治疗中免疫抑制剂的应用[J]. 临床肝胆病杂志, 2018, 34: 1614-1618. doi: 10.3969/j.issn.1001-5256.2018.08.005 [12] van der Neut Kolfschoten M, Schuurman J, Losen M, et al. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange[J]. Science, 2007, 317: 1554-1557. doi: 10.1126/science.1144603 [13] Hubers LM, Vos H, Schuurman AR, et al. Annexin A11 is targeted by IgG4 and IgG1 autoantibodies in IgG4-related disease[J]. Gut, 2018, 67: 728-735. [14] Shiokawa M, Kodama Y, Kuriyama K, et al. Pathogenicity of IgG in patients with IgG4-related disease[J]. Gut, 2016, 65: 1322-1332. doi: 10.1136/gutjnl-2015-310336 [15] Wallace ZS, Mattoo H, Carruthers M, et al. Plasmablasts as a biomarker for IgG4-related disease, independent of serum IgG4 concentrations[J]. Ann Rheum Dis, 2015, 74: 190-195. doi: 10.1136/annrheumdis-2014-205233 [16] Della-Torre E, Rigamonti E, Perugino C, et al. B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease[J]. J Allergy Clin Immunol, 2020, 145: 968-981. doi: 10.1016/j.jaci.2019.07.004 [17] Maillette de Buy Wenniger LJ, Doorenspleet ME, Klarenbeek PL, et al. Immunoglobulin G4+ clones identified by next-generation sequencing dominate the B cell receptor repertoire in immunoglobulin G4 associated cholangitis[J]. Hepatology (Baltimore, Md), 2013, 57: 2390-2398. doi: 10.1002/hep.26232 [18] Sumimoto K, Uchida K, Kusuda T, et al. The role of CD19+CD24highCD38high and CD19+CD24highCD27+ regulatory B cells in patients with type 1 autoimmune pancreatitis[J]. Pancreatology, 2014, 14: 193-200. doi: 10.1016/j.pan.2014.02.004 [19] Akitake R, Watanabe T, Zaima C, et al. Possible involvement of T helper type 2 responses to Toll-like receptor ligands in IgG4-related sclerosing disease[J]. Gut, 2010, 59: 542-545. doi: 10.1136/gut.2009.200972 [20] Suzuki K, Tamaru J, Okuyama A, et al. IgG4-positive multi-organ lymphoproliferative syndrome manifesting as chronic symmetrical sclerosing dacryo-sialadenitis with subsequent secondary portal hypertension and remarkable IgG4-linked IL-4 elevation[J]. Rheumatology (Oxford), 2010, 49: 1789-1791. doi: 10.1093/rheumatology/keq113 [21] Meiler F, Klunker S, Zimmermann M, et al. Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors[J]. Allergy, 2008, 63: 1455-1463. doi: 10.1111/j.1398-9995.2008.01774.x [22] Maehara T, Mattoo H, Ohta M, et al. Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis[J]. Ann Rheum Dis, 2017, 76: 377-385. doi: 10.1136/annrheumdis-2016-209139 [23] Mattoo H, Mahajan VS, Maehara T, et al. Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease[J]. J Allergy Clin Immunol, 2016, 138: 825-838. doi: 10.1016/j.jaci.2015.12.1330 [24] Pillai S, Perugino C, Kaneko N. Immune mechanisms of fibrosis and inflammation in IgG4-related disease[J]. Curr Opin Rheumatol, 2020, 32: 146-151. doi: 10.1097/BOR.0000000000000686 [25] Boonpiyathad T, Satitsuksanoa P, Akdis M, et al. IL-10 producing T and B cells in allergy[J]. Semin Immunol, 2019, 44: 101326. doi: 10.1016/j.smim.2019.101326 [26] Kusuda T, Uchida K, Miyoshi H, et al. Involvement of inducible costimulator-and interleukin 10-positive regulatory T cells in the development of IgG4-related autoimmune pancreatitis[J]. Pancreas, 2011, 40: 1120-1130. doi: 10.1097/MPA.0b013e31821fc796 [27] Akiyama M, Suzuki K, Kassai Y, et al. Resolution of elevated circulating regulatory T cells by corticosteroids in patients with IgG4-related dacryoadenitis and sialoadenitis[J]. Int J Rheum Dis, 2016, 19: 430-432. doi: 10.1111/1756-185X.12725 [28] Miyoshi H, Uchida K, Taniguchi T, et al. Circulating naïve and CD4+CD25high regulatory T cells in patients with autoimmune pancreatitis[J]. Pancreas, 2008, 36: 133-140. doi: 10.1097/MPA.0b013e3181577553 [29] Mattoo H, Mahajan VS, Della-Torre E, et al. De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease[J]. J Allergy Clin Immunol, 2014, 134: 679-687. doi: 10.1016/j.jaci.2014.03.034 [30] Maehara T, Mattoo H, Mahajan VS, et al. The expansion in lymphoid organs of IL-4(+) BATF(+) T follicular helper cells is linked to IgG4 class switching in vitro[J]. Life Sci Alliance, 2018, 1: e201800050. doi: 10.26508/lsa.201800050 [31] Akiyama M, Yasuoka H, Yoshimoto K, et al. Interleukin-4 contributes to the shift of balance of IgG subclasses toward IgG4 in IgG4-related disease[J]. Cytokine, 2018, 110: 416-419. doi: 10.1016/j.cyto.2018.05.009 [32] Zhang J, Lian M, Li B, et al. Interleukin-35 Promotes Th9 Cell Differentiation in IgG4-Related Disorders: Experimental Data and Review of the Literature[J]. Clin Rev Allergy Immunol, 2021, 60: 132-145. doi: 10.1007/s12016-020-08803-8 [33] Xia C, Liu C, Liu Y, et al. Increased Circulating Th1 and Tfh1 Cell Numbers Are Associated with Disease Activity in Glucocorticoid-Treated Patients with IgG4-Related Disease[J]. J Immunol Res, 2020, 2020: 3757015. [34] Moriyama M, Nakamura S. Th1/Th2 Immune Balance and Other T Helper Subsets in IgG4-Related Disease[J]. Curr Top Microbiol Immunol, 2017, 401: 75-83. [35] Siegal FP, Kadowaki N, Shodell M, et al. The nature of the principal type 1 interferon-producing cells in human blood[J]. Science, 1999, 284: 1835-1837. doi: 10.1126/science.284.5421.1835 [36] Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity[J]. Immunity, 2011, 34: 637-650. doi: 10.1016/j.immuni.2011.05.006 [37] Blasius AL, Beutler B. Intracellular toll-like receptors[J]. Immunity, 2010, 32: 305-315. doi: 10.1016/j.immuni.2010.03.012 [38] Honda K, Takaoka A, Taniguchi T. Type Ⅰ interferon[corrected] gene induction by the interferon regulatory factor family of transcription factors[J]. Immunity, 2006, 25: 349-360. doi: 10.1016/j.immuni.2006.08.009 [39] Kawai T, Sato S, Ishii KJ, et al. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6[J]. Nat Immunol, 2004, 5: 1061-1068. doi: 10.1038/ni1118 [40] Watanabe T, Asano N, Fichtner-Feigl S, et al. NOD1 contributes to mouse host defense against Helicobacter pylori via induction of type Ⅰ IFN and activation of the ISGF3 signaling pathway[J]. J Clin Invest, 2010, 120: 1645-1662. doi: 10.1172/JCI39481 [41] Minaga K, Watanabe T, Hara A, et al. Plasmacytoid Dendritic Cells as a New Therapeutic Target for Autoimmune Pancreatitis and IgG4-Related Disease[J]. Front Immunol, 2021, 12: 713779. doi: 10.3389/fimmu.2021.713779 [42] Arai Y, Yamashita K, Kuriyama K, et al. Plasmacytoid Dendritic Cell Activation and IFN-α Production Are Prominent Features of Murine Autoimmune Pancreatitis and Human IgG4-Related Autoimmune Pancreatitis[J]. J Immunol, 2015, 195: 3033-3044. doi: 10.4049/jimmunol.1500971 [43] Kamata K, Watanabe T, Minaga K, et al. Intestinal dysbiosis mediates experimental autoimmune pancreatitis via activation of plasmacytoid dendritic cells[J]. Int Immunol, 2019, 31: 795-809. doi: 10.1093/intimm/dxz050 [44] Watanabe T, Minaga K, Kamata K, et al. Mechanistic Insights into Autoimmune Pancreatitis and IgG4-related Disease[J]. Trends Immunol, 2018, 39: 874-889. doi: 10.1016/j.it.2018.09.005 [45] Watanabe T, Yamashita K, Arai Y, et al. Chronic Fibro-Inflammatory Responses in Autoimmune Pancreatitis Depend on IFN-α and IL-33 Produced by Plasmacytoid Dendritic Cells[J]. J Immunol, 2017, 198: 3886-3896. doi: 10.4049/jimmunol.1700060 [46] Moriyama M, Nakamura S. Potential Pathways in the Pathogenesis of IgG4-Related Disease[M]. Tokyo: Springer Japan, 2016: 43-54. [47] Qureshi A, Ghobrial Y, De Castro J, et al. Autoimmune pancreatitis-What we know and what do we have to know?[J]. Autoimmun Rev, 2021, 20: 102912. doi: 10.1016/j.autrev.2021.102912 [48] Chang YJ, Kim HY, Albacker LA, et al. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity[J]. Nat Immunol, 2011, 12: 631-638. doi: 10.1038/ni.2045 [49] Baenziger S, Heikenwalder M, Johansen P, et al. Trigger-ing TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology[J]. Blood, 2009, 113: 377-388. doi: 10.1182/blood-2008-04-151712 [50] Tsuboi H, Nakai Y, Iizuka M, et al. DNA microarray analysis of labial salivary glands in IgG4-related disease: comparison with Sj gren's syndrome[J]. Arthritis Rheumatol, 2014, 66: 2892-2899. doi: 10.1002/art.38748 [51] Akiyama M, Yasuoka H, Yoshimoto K, et al. CC-chemokine ligand 18 is a useful biomarker associated with disease activity in IgG4-related disease[J]. Ann Rheum Dis, 2018, 77: 1386-1387. doi: 10.1136/annrheumdis-2017-212110 [52] Schwartz C, Eberle JU, Voehringer D. Basophils in inflammation[J]. Eur J Pharmacol, 2016, 778: 90-95. doi: 10.1016/j.ejphar.2015.04.049 [53] Watanabe T, Yamashita K, Fujikawa S, et al. Involvement of activation of toll-like receptors and nucleotide-binding oligomerization domain-like receptors in enhanced IgG4 responses in autoimmune pancreatitis[J]. Arthritis Rheum, 2012, 64: 914-924. doi: 10.1002/art.33386 [54] Bieneman AP, Chichester KL, Chen YH, et al. Toll-like receptor 2 ligands activate human basophils for both IgE-dependent and IgE-independent secretion[J]. J Allergy Clin Immunol, 2005, 115: 295-301. doi: 10.1016/j.jaci.2004.10.018 [55] Egawa M, Mukai K, Yoshikawa S, et al. Inflammatory monocytes recruited to allergic skin acquire an anti-inflammatory M2 phenotype via basophil-derived interleukin-4[J]. Immunity, 2013, 38: 570-580. doi: 10.1016/j.immuni.2012.11.014 [56] Shiokawa M, Kodama Y, Sekiguchi K, et al. Laminin 511 is a target antigen in autoimmune pancreatitis[J]. Sci Transl Med, 2018, 10: eaaq0997. doi: 10.1126/scitranslmed.aaq0997 [57] Perugino CA, AlSalem SB, Mattoo H, et al. Identification of galectin-3 as an autoantigen in patients with IgG(4)-related disease[J]. J Allergy Clin Immunol, 2019, 143: 736-745. doi: 10.1016/j.jaci.2018.05.011 -
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