CD69 Regulates Type I IFN-Induced Tolerogenic Signals to Mucosal CD4 T Cells That Attenuate Their Colitogenic Potential
CD69 Regulates Type I IFN-Induced Tolerogenic Signals to Mucosal CD4 T Cells That Attenuate Their Colitogenic Potential
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DOI：
10.4049/jimmunol.1100765
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发表时间：
2012-02-15
影响因子：
4.4
通讯作者：
Niess, Jan Hendrik
中科院分区：
文献类型：
--
作者：
Radulovic, Katarina;Manta, Calin;Niess, Jan Hendrik
CD 69由粘膜表面的淋巴细胞高度表达。我们的目的是研究CD 69在粘膜免疫反应中的作用。在无特定病原体的B6和TCR转基因动物以及无菌B6小鼠中，测定了从脾脏、肠系膜淋巴结、小肠固有层和结肠固有层分离的CD 4 T细胞的CD 69表达。通过向RAG（-/-）小鼠移植B6或CD 69（-/-）CD 45 RB（高）CD 4 T细胞诱导转移性结肠炎。CD 4 T细胞的CD 69表达是由肠道微生物菌群、口服特异性抗原和型！IFN（IFN-I）信号。来自CD 69（-/-）动物的CD 4 T细胞产生更大量的促炎细胞因子IFN-γ、TNF-α和IL-21，而TGF-β 1的产生减少。CD 69缺陷型CD 4 T细胞在体内和体外分化为Foxp 3（+）调节性T细胞的潜力降低。将CD 69（-/-）CD 45 RB（高）CD 4 T细胞转移到RAG（-/-）宿主中诱导加速结肠炎。与B6和OT-H x RAG（-/-）动物相比，CD 69（-/-）和IFN-I受体1缺陷小鼠的口服耐受性受损。多聚肌苷酸-多聚胞苷酸治疗RAG（-/-）小鼠，移植B6而非CD 69（-/-）或IFN-1受体1缺陷型CD 45 RB（高）CD 4 T细胞，可减轻转移性结肠炎。CD 69缺陷导致促炎细胞因子产生增加，Foxp 3（+）调节性T细胞诱导减少，口服耐受性受损，结肠炎更严重。因此，活化Ag CD 69在调节粘膜免疫应答中起重要作用。免疫学杂志，2012，188：2001-2013。
CD69 is highly expressed by lymphocytes at mucosal surfaces. We aimed to investigate the role of CD69 in mucosal immune responses. The expression of CD69 by CD4 T cells isolated from the spleen, mesenteric lymph nodes, small intestinal lamina propria, and colonic lamina propria was determined in specific pathogen-free B6 and TCR transgenic animals, as well as in germ-free B6 mice. Transfer colitis was induced by transplanting RAG(-/-) mice with B6 or CD69(-/-)CD45RB(high) CD4 T cells. CD69 expression by CD4 T cells is induced by the intestinal microflora, oral delivery of specific Ag, and type! IFN (IFN-I) signals. CD4 T cells from CD69(-/-) animals produce higher amounts of the proinflammatory cytokines IFN-gamma, TNF-alpha, and IL-21, whereas the production of TGF-beta 1 is decreased. CD69-deficient CD4 T cells showed reduced potential to differentiate into Foxp3(+) regulatory T cells in vivo and in vitro. The transfer of CD69(-/-)CD45RB(high) CD4 T cells into RAG(-/-) hosts induced an accelerated colitis. Oral tolerance was impaired in CD69(-/-) and IFN-I receptor 1-deficient mice when compared with B6 and OT-H x RAG(-/-) animals. Polyinosinic-polycytidylic acid treatment of RAG(-/-) mice transplanted with B6 but not CD69(-/-) or IFN-I receptor 1-deficient CD45RB(high) CD4 T cells attenuated transfer colitis. CD69 deficiency led to the increased production of proinflammatory cytokines, reduced Foxp3(+) regulatory T cell induction, impaired oral tolerance, and more severe colitis. Hence, the activation Ag CD69 plays an important role in regulating mucosal immune responses. The Journal of Immunology, 2012, 188: 2001-2013.