CXCR6+ST2+ memory T helper 2 cells induced the expression of major basic protein in eosinophils to reduce the fecundity of helminth
CXCR6+ST2+ memory T helper 2 cells induced the expression of major basic protein in eosinophils to reduce the fecundity of helminth
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CXCR6 ST2记忆辅助T细胞2诱导嗜酸性粒细胞主要碱性蛋白表达降低蠕虫繁殖力
DOI：
10.1073/pnas.1714731115
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
T.
中科院分区：
文献类型：
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作者：
Obata-Ninomiya;K.;Ishiwata;K.;Nakano;H.;Endo;Y.;Ichikawa;T.;Onodera;A.;Hirahara;K.;Okamoto;Y.;Kanuka;H.;Nakayama;T.
记忆性辅助性T细胞（mTh）在病原体的再感染中起重要作用，并驱动疾病的发病机制。虽然最近的研究已经表征了驱动过敏性炎症的致病性mTh 2细胞亚群，但那些诱导针对蠕虫感染的免疫应答的细胞亚群仍然未知。我们发现，产生IL-5的CXCR 6 + ST 2 + CD 44 + mTh 2细胞在IL-33依赖性抑制蠕虫繁殖力中起着至关重要的作用，而其他ST 2 − mTh 2细胞则没有。虽然两种细胞类型诱导粒细胞，特别是嗜酸性粒细胞浸润到肺部，以响应蠕虫感染，ST 2 + mTh 2细胞诱导的嗜酸性粒细胞表达更高水平的主要碱性蛋白（MBP），这对降低Nippostrongylus brasiliensis（Nb）的繁殖力很重要，而不是ST 2 − mTh 2细胞诱导的。值得注意的是，我们还发现ST 2 +Treg细胞而不是ST 2 −Treg细胞抑制CXCR 6 + ST 2 + mTh 2细胞介导的免疫应答。综上所述，这些发现表明，我们确定了一种抗蠕虫的机制，该机制由产生IL-5的mTh 2细胞亚群通过在肺中强烈表达MBP的嗜酸性粒细胞的积累引起。
Memory T helper (mTh) cells play important roles in the reinfection of pathogens and drive the pathogenesis of diseases. While recent studies have characterized the pathogenic mTh2 cell subpopulations driving allergic inflammation, those that induce immune responses against helminth infection remain unknown. We found that IL-5–producing CXCR6+ST2+CD44+mTh2 cells play a crucial role in the IL-33–dependent inhibition of the fecundity of helminth, whereas other ST2−mTh2 cells do not. Although both cell types induced the infiltration of granulocytes, especially eosinophils, into the lungs in response to helminth infection, the ST2+mTh2 cell-induced eosinophils expressed higher levels of major basic protein (MBP), which is important for reducing the fecundity ofNippostrongylus brasiliensis(Nb), than ST2−mTh2 cell-induced ones. Notably, we also found that ST2+Treg cells but not ST2−Treg cells suppressed CXCR6+ST2+mTh2 cell-mediated immune responses. Taken together, these findings show that we identified a mechanism against helminth elicited by a subpopulation of IL-5–producing mTh2 cells through the accumulation of eosinophils strongly expressing MBP in the lungs.