Department of Immunology, The Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
St Vincent's Clinical School, University of NSW, Sydney, NSW, Australia.
Front Immunol. 2019 Jan 4;9:2899. doi: 10.3389/fimmu.2018.02899. eCollection 2018.
CD4 T helper (Th) cells that express the gut homing chemokine receptor CCR9 are increased in the peripheral blood of patients with inflammatory bowel disease and Sjögren's syndrome and in the inflamed lesions of autoimmune diseases that affect the accessory organs of the digestive system. However, despite the important role of the GIT in both immunity and autoimmunity, the nature of CCR9-expressing cells in GIT lymphoid organs and their role in chronic inflammatory diseases remains unknown. In this study, we analyzed the characteristics of CCR9 Th and T follicular helper (Tfh) cells in GIT associated lymphoid tissues in health, chronic inflammation and autoimmunity. Our findings reveal an association between the transcriptome and phenotype of CCR9 Th in the pancreas and CCR9 Tfh cells from GIT-associated lymphoid tissues. GIT CCR9 Tfh cells exhibited characteristics, including a Th17-like transcriptome and production of effector cytokines, which indicated a microenvironment-specific signature. Both CCR9 Tfh cells and CCR9 Th cells from GIT-associated lymphoid tissues migrated to the pancreas. The expression of CCR9 was important for migration of both subsets to the pancreas, but Tfh cells that accumulated in the pancreas had downmodulated expression of CXCR5. Taken together, the findings provide evidence that CCR9 Tfh cells and Th cells from the GIT exhibit plasticity and can accumulate in distal accessory organs of the digestive system where they may participate in autoimmunity.
表达肠道归巢趋化因子受体 CCR9 的 CD4 T 辅助 (Th) 细胞在炎症性肠病和干燥综合征患者的外周血中以及影响消化系统附属器官的自身免疫性疾病的炎症病变中增加。然而，尽管 GIT 在免疫和自身免疫中都具有重要作用，但 GIT 淋巴器官中 CCR9 表达细胞的性质及其在慢性炎症性疾病中的作用仍不清楚。在这项研究中，我们分析了健康、慢性炎症和自身免疫中与 GIT 相关的淋巴组织中 CCR9 Th 和滤泡辅助 T (Tfh) 细胞的特征。我们的研究结果揭示了胰腺中 CCR9 Th 的转录组和表型与来自 GIT 相关淋巴组织的 CCR9 Tfh 细胞之间的关联。GIT CCR9 Tfh 细胞表现出特征，包括 Th17 样转录组和效应细胞因子的产生，这表明存在特定于微环境的特征。来自 GIT 相关淋巴组织的 CCR9 Tfh 细胞和 CCR9 Th 细胞均迁移到胰腺。CCR9 的表达对于这两个亚群向胰腺的迁移都很重要，但在胰腺中积累的 Tfh 细胞下调了 CXCR5 的表达。总之，这些发现提供了证据，表明来自 GIT 的 CCR9 Tfh 细胞和 Th 细胞具有可塑性，可以在消化系统的远端附属器官中积累，在那里它们可能参与自身免疫。
