Liu Han, Chen Feidi, Wu Wei, Cao Anthony T, Xue Xiaochang, Yao Suxia, Evans-Marin Heather L, Li Yan-Qing, Cong Yingzi
Department of Gastroenterology, The Qilu Hospital, Shandong University, Shandong, China.
Department of Microbiology and Immunology, and University of Texas Medical Branch, USA.
Sci Rep. 2016 Feb 24;6:22040. doi: 10.1038/srep22040.
Multiple mechanisms exist in regulation of host responses to massive challenges from microbiota to maintain immune homeostasis in the intestines. Among these is the enriched Th17 cells in the intestines, which regulates intestinal homeostasis through induction of antimicrobial peptides and secretory IgA among others. However, the means by which Th17 cells develop in response to microbiota is still not completely understood. Although both TLR5 and CD172α(+) lamina propria dendritic cells (LPDC) have been shown to promote Th17 cell development, it is still unclear whether TLR5 mediates the CD172α(+)LPDC induction of Th17 cells. By using a microbiota antigen-specific T cell reporter mouse system, we demonstrated that microbiota antigen-specific T cells developed into Th17 cells in the intestinal LP, but not in the spleen when transferred into TCRβxδ(-/-) mice. LPDCs expressed high levels of TLR5, and most CD172α(+)LPDCs also co-expressed TLR5. LPDCs produced high levels of IL-23, IL-6 and TGFβ when stimulated with commensal flagellin and promoted Th17 cell development when cultured with full-length CBir1 flagellin but not CBir1 peptide. Wild-type CD172α(+), but not CD172α(-), LPDCs induced Th17 cells, whereas TLR5-deficient LPDC did not induce Th17 cells. Our data thereby demonstrated that TLR5 mediates CD172α(+)LPDC induction of Th17 cells in the intestines.
在宿主应对微生物群的巨大挑战以维持肠道免疫稳态的过程中，存在多种调节机制。其中包括肠道中富集的Th17细胞，它通过诱导抗菌肽和分泌型IgA等调节肠道稳态。然而，Th17细胞响应微生物群而发育的方式仍未完全了解。虽然TLR5和CD172α(+)固有层树突状细胞(LPDC)均已被证明可促进Th17细胞发育，但TLR5是否介导CD172α(+)LPDC对Th17细胞的诱导仍不清楚。通过使用微生物群抗原特异性T细胞报告小鼠系统，我们证明，当转移到TCRβxδ(-/-)小鼠体内时，微生物群抗原特异性T细胞在肠道固有层发育为Th17细胞，而在脾脏中则不然。LPDC表达高水平的TLR5，并且大多数CD172α(+)LPDC也共表达TLR5。在用共生鞭毛蛋白刺激时，LPDC产生高水平的IL-23、IL-6和TGFβ，并且在与全长CBir1鞭毛蛋白而非CBir1肽一起培养时促进Th17细胞发育。野生型CD172α(+)而非CD172α(-)LPDC诱导Th17细胞，而TLR5缺陷型LPDC不诱导Th17细胞。因此，我们的数据证明TLR5介导肠道中CD172α(+)LPDC对Th17细胞的诱导。
