Department of Immunology, School of Basic Medical Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Department of Pathology, The University of Hong Kong, Hong Kong, China.
Immunology. 2018 Nov;155(3):356-366. doi: 10.1111/imm.12977. Epub 2018 Jul 26.
Regulatory T (Treg) cells play an essential role in the maintenance of intestinal homeostasis. In Peyer's patches (PPs), which comprise the most important IgA induction site in the gut-associated lymphoid tissue, Treg cells promote IgA isotype switching. However, the mechanisms underlying their entry into PPs and isotype switching facilitation in activated B cells remain unknown. This study, based on the dextran sulphate sodium (DSS)-induced colitis model, revealed that Treg cells are significantly increased in PPs, along with CD11b B-cell induction. Immunofluorescence staining showed that infiltrated Treg cells were located around CD11b B cells and produced transforming growth factor-β, thereby inducing IgA B cells. Furthermore, in vivo and in vitro studies revealed that CD11b B cells in PPs had the capacity to recruit Treg cells into PPs rather than promoting their proliferation. Finally, we found that Treg cell recruitment was mediated by the chemokine CXCL9 derived from CD11b B cells in PPs. These findings demonstrate that CD11b B cells induced in PPs during colitis actively recruit Treg cells to accomplish IgA isotype switch in a CXCL9-dependent manner.
调节性 T(Treg)细胞在维持肠道内稳态中发挥着重要作用。在派尔集合淋巴结(PPs)中,Treg 细胞促进 IgA 同种型转换,它是肠道相关淋巴组织中最重要的 IgA 诱导部位。然而,Treg 细胞进入 PPs 并促进活化 B 细胞同种型转换的机制尚不清楚。本研究基于葡聚糖硫酸钠(DSS)诱导的结肠炎模型,揭示了 Treg 细胞在 PPs 中显著增加,同时伴有 CD11b B 细胞诱导。免疫荧光染色显示,浸润的 Treg 细胞位于 CD11b B 细胞周围,并产生转化生长因子-β,从而诱导 IgA B 细胞。此外,体内和体外研究表明,PPs 中的 CD11b B 细胞具有招募 Treg 细胞进入 PPs 的能力,而不是促进其增殖。最后,我们发现 Treg 细胞的招募是由 PPs 中的 CD11b B 细胞产生的趋化因子 CXCL9 介导的。这些发现表明,结肠炎时 PPs 中诱导的 CD11b B 细胞通过依赖于 CXCL9 的方式主动招募 Treg 细胞来完成 IgA 同种型转换。