Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis
Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis
复制标题
DOI：
10.1007/s00535-020-01689-5
复制
发表时间：
2020-05
影响因子：
6.3
通讯作者：
Takashi Ito;Toshihiro Tanaka;Koh Nakamaru;T. Tomiyama;Takashi Yamaguchi;Y. Ando;T. Ikeura;T. Fukui;K. Uchida;A. Nishio;K. Okazaki
中科院分区：
文献类型：
--
作者：
Takashi Ito;Toshihiro Tanaka;Koh Nakamaru;T. Tomiyama;Takashi Yamaguchi;Y. Ando;T. Ikeura;T. Fukui;K. Uchida;A. Nishio;K. Okazaki
背景：IgG4相关疾病(IgG4-RD)是一种全身性炎症性疾病，包括1型自身免疫性胰腺炎(AIP)。白介素35(IL-35)在多种自身免疫性疾病中具有免疫抑制作用。然而，到目前为止，IL-35在1型AIP中的表达尚未见报道。方法收集1型AIP患者、慢性酒精性胰腺炎(ACP)患者和健康对照组(HC)的血浆，检测细胞因子的表达。从幼稚树(NTregs)和效应树(ETregs)提取外周血总mRNA，用定量聚合酶链式反应检测EBI3和IL-12p35基因的表达。结果1型急性胰腺炎患者(n= ，32例)血浆IL-35水平明显高于急性胰腺炎(n= ，n=16)和慢性胰腺炎(n= ，22例)，而IL-27无明显变化。我们还在1型AIP组织中检测到许多同时表达EBI3和IL-12p35的细胞。此外，1型 患者(n= 14)外周血中T细胞亚群nTregs和eTregs的百分率均显著低于HC(n=Hc15)。结论1型AIP患者血浆IL-35和组织IL-35亚单位的表达水平明显升高。这可能通过激活eTregs来抑制炎症。IL-35可能与这种抗炎作用有关，尤其是通过几种细胞因子和1型AIP中Tregs的分化来对抗Th2反应。
BackgroundIgG4-related disease (IgG4-RD) is a systemic inflammatory disease, which includes type 1 autoimmune pancreatitis (AIP). Interleukin-35 (IL-35) exhibits immunosuppressive effects in several autoimmune diseases. However, the expression of IL-35 had not been reported so far in type 1 AIP. We evaluated the association between IL-35 and several cytokines, which mediate the function of Tregs in type 1 AIP.MethodsPlasma was collected from patients with type 1 AIP, alcoholic chronic pancreatitis (ACP), and healthy controls (HC) and assayed for cytokine expression. Total mRNA separated from peripheral blood was isolated from naïve Tregs (nTregs) and effector Tregs (eTregs).EBI3andIL-12p35gene expressions were tested in these cells by quantitative PCR. In addition, expression of IL-35 subunits in the pancreatic tissues of patients with type 1 AIP and ACP was analyzed by immunohistochemistry.ResultsIL-35 was significantly elevated in type 1 AIP (n= 32) plasma compared with ACP (n= 16) and HC (n= 22), but IL-27 was not. We also detected many cells expressing both EBI3 and IL-12p35 in type 1 AIP tissues. Moreover, in peripheral blood lymphocyte, the percentage of nTregs and eTregs of CD4+T cells in patients with type 1 AIP (n= 14) compared with HC (n= 15) was significantly decreased and increased, respectively. There were no significant differences of gene expression in patients with type 1 AIP and HC.ConclusionsThis study identified elevated expression of plasma IL-35 and tissue IL-35 subunits in patients with type 1 AIP. This might lead to inflammation suppression via activated eTregs. IL-35 might be associated with this anti-inflammatory role, especially against the Th2 response through several cytokines and the differentiation of Tregs in type 1 AIP.