法国巴黎文理研究大学Olivier Lantz小组在研究中取得进展。他们发现微生物代谢产物能够调控粘膜相关恒定T细胞（MAIT）的胸腺发育。这一研究成果发表在2019年8月30日出版的国际学术期刊《科学》上。

研究人员发现共生细菌控制小鼠MAIT在胸腺内的发育，因为MAIT细胞是不再循环到胸腺的。MAIT发育需要细菌中的RibD表达，这表明MAIT抗原5-OP-RU（5-(2-oxopropylideneamino)-6-D-ribitylaminouracil）的产生是必需的。5-OP-RU迅速从粘膜表面转移到胸腺，在那里它被MHC Ib分子MR1捕获。这导致最早的MAIT前体细胞数量的增加以及更成熟的RORγt（receptor–related orphan receptor γt）阳性MAIT细胞的扩增。 因此，微生物菌群来源的代谢物控制粘膜靶向T细胞的发育，这一过程模糊了外源性和自身抗原之间的区别。

据了解，微生物菌群如何调节免疫功能仍然知之甚少。MAIT与粘膜稳态有关，这在无菌小鼠中不存在。

Title: Microbial metabolites control the thymic development of mucosal-associated invariant T cells

Author: Franois Legoux, Déborah Bellet, Celine Daviaud, Yara El Morr, Aurelie Darbois, Kristina Niort, Emanuele Procopio, Marion Salou, Jules Gilet, Bernhard Ryffel, Aurélie Balvay, Anne Foussier, Manal Sarkis, Ahmed El Marjou, Frederic Schmidt, Sylvie Rabot, Olivier Lantz

Issue&Volume: 2019/09/13

Abstract: How the microbiota modulate immune functions remains poorly understood. Mucosal-associated invariant T (MAIT) cells are implicated in mucosal homeostasis and absent in germ-free mice. Here, we show that commensal bacteria govern murine MAIT intrathymic development, as MAIT cells did not recirculate to the thymus. MAIT development required RibD expression in bacteria, indicating that production of the MAIT antigen 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) was necessary. 5-OP-RU rapidly traveled from mucosal surfaces to the thymus, where it was captured by the major histocompatibility complex class Ib molecule MR1. This led to increased numbers of the earliest MAIT precursors and the expansion of more mature receptor–related orphan receptor γt–positive MAIT cells. Thus, a microbiota-derived metabolite controls development of mucosally targeted T cells, in a process blurring the distinction between exogenous and self-antigens.

DOI: 10.1126/science.aaw2719

Source: https://science.sciencemag.org/content/early/2019/08/28/science.aaw2719