Recent Advances in Understanding the Role of TIGIT+ Follicular Helper T Cells in IgG4-Related Disease
Recent Advances in Understanding the Role of TIGIT+ Follicular Helper T Cells in IgG4-Related Disease
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DOI：
10.3390/immuno1040026
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发表时间：
2021-10
期刊：
影响因子：
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通讯作者：
M. Akiyama;Y. Kaneko
中科院分区：
文献类型：
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作者：
M. Akiyama;Y. Kaneko
IgG 4相关疾病（IgG 4-RD）是一种纤维炎性疾病，其特征在于血清IgG 4水平升高和IgG 4+浆细胞大量浸润。虽然Storiform纤维化，闭塞性静脉炎和IgG 4+浆细胞浸润是很好地描述了这种疾病的病理特征，三级淋巴样器官（TLO）的过度形成，特别是在疾病病变的早期阶段，已经得到了很多关注。IgG 4-RD的TLO由特异性免疫细胞亚群协调，包括滤泡辅助T细胞（Tfh）、CD 20 + B细胞和CD 21+滤泡树突细胞（FDC）。Tfh是这种疾病的关键参与者，因为最近的研究表明这种免疫细胞亚群在形成TLO、帮助IgG 4+浆细胞分化、通过分泌白细胞介素-4诱导风暴状纤维化和通过分泌白细胞介素-21激活细胞毒性T细胞中的病理作用。我们最近鉴定了一个新的Tfh亚群，其表达具有免疫球蛋白和ITIM结构域的T细胞免疫受体（TIGIT）。TIGIT+Tfh通过0X 40信号有效地产生白细胞介素-21，并且外周TIGIT+Tfh细胞的增加反映了IgG 4-RD中的疾病活性。TIGIT对于通过与⑶ 21 + FDC上表达的⑶ 155相互作用介导TIGIT+Tfh在TLO内的保留和定位是重要的。本文就近年来对IgG 4-RD发病机制的研究进展作一综述，重点介绍TIGIT+Tfh。
IgG4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by elevated serum IgG4 levels and massive infiltration of IgG4+plasma cells. Although storiform fibrosis, obliterative phlebitis and IgG4+plasma cell infiltration are well described pathological features in this disease, the excessive formation of tertiary lymphoid organs (TLOs), particularly in the early phase of the disease lesions, has gained much attention. TLOs of IgG4-RD are orchestrated by specific immune cell subsets including follicular helper T cells (Tfh), CD20+ B cells, and CD21+ follicular dendritic cells (FDCs). Tfh is the key player of this disease because recent studies have suggested the pathological role of this immune cell subset in formation of TLOs, helping IgG4+plasma cell differentiation, inducing storiform fibrosis by secreting interleukin-4, and activating cytotoxic T cells by secreting interleukin-21. We have recently identified a new Tfh subset which expresses T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT). TIGIT+Tfh efficiently produces interleukin-21 through OX40 signal, and the increase in peripheral TIGIT+Tfh cells reflects disease activity in IgG4-RD. TIGIT is important to mediate the retention and positioning of TIGIT+Tfh within TLOs through interaction with CD155 expressed on CD21+ FDCs. In this review, we summarize and discuss recent progress in understanding the pathogenesis of IgG4-RD, focusing on TIGIT+Tfh.