MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation.

MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation.
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DOI:
10.1038/mi.2016.30
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发表时间:
2017-01
期刊:
影响因子:
8
通讯作者:
Tjernlund A
Tjernlund A
中科院分区:
医学1区
文献类型:
--
作者:
Gibbs A;Leeansyah E;Introini A;Paquin-Proulx D;Hasselrot K;Andersson E;Broliden K;Sandberg JK;Tjernlund A

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女性生殖道(FGT)粘膜是对微生物进行免疫防御的重要部位。mucal -associated invariant T (MAIT)细胞是一种先天样T细胞群,以mr1依赖的方式识别微生物核黄素代谢物抗原。MAIT细胞在FGT粘膜中的作用尚不清楚。在这里,我们发现MAIT细胞和MR1+抗原呈递细胞存在于FGT的上部和下部,并且MAIT细胞在子宫内膜和子宫颈的组织定位不同。来自FGT和血液的MAIT细胞表现出不同的表型,表达IL-18Rα、CD127、α4β7、PD-1以及转录因子PLZF、RORγt、Helios、Eomes和T-bet。与血液相比,FGT中PLZF和Eomes的表达水平较低。当受到大肠杆菌的刺激时,来自FGT的MAIT细胞表现出对IL-17和IL-22表达的偏好,而血液中的MAIT细胞主要产生IFN-γ、TNF和颗粒酶b。此外,FGT和血液来源的MAIT细胞都是多功能的,并参与了T细胞介导的大肠杆菌反应。因此,生殖粘膜中的MAIT细胞具有不同的IL-17/IL-22谱,可能在该部位的免疫稳态和微生物控制中发挥重要作用。
The female genital tract (FGT) mucosa is a critically important site for immune defense against microbes. Mucosal-associated invariant T (MAIT) cells are an innate-like T cell population that recognizes microbial riboflavin metabolite antigens in an MR1-dependent manner. The role of MAIT cells in the FGT mucosa is unknown. Here, we found that MAIT cells and MR1+ antigen-presenting cells were present in the upper and lower FGT, with distinct tissue localization of MAIT cells in endometrium versus cervix. MAIT cells from the FGT and blood displayed a distinct phenotype with expression of IL-18Rα, CD127, α4β7, PD-1, as well as the transcription factors PLZF, RORγt, Helios, Eomes and T-bet. Their expression levels of PLZF and Eomes were lower in the FGT compared to blood. When stimulated with Escherichia coli, MAIT cells from the FGT displayed a bias towards IL-17 and IL-22 expression, whereas blood MAIT cells produced primarily IFN-γ, TNF, and Granzyme B. Furthermore, both FGT- and blood-derived MAIT cells were polyfunctional and contributed to the T cell-mediated response to E. coli. Thus, MAIT cells in the genital mucosa have a distinct IL-17/IL-22 profile and may play an important role in immunological homeostasis and control of microbes at this site.