期刊
JOURNAL OF IMMUNOLOGY
卷 192, 期 10, 页码 4655-4665出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1400121
关键词
-
类别
资金
- U.S. Public Health Service [R01 18919]
- National Institutes of Health [R01 AI076575-01]
- National Institutes of Health Director's New Innovator award [DP2OD002230]
- Canadian Institutes of Health Research MOP [125933]
- National Research Foundation of Korea-Global Research Network [2013S1A2A2035348]
- National Research Foundation of Korea [2013S1A2A2035348] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
In murine schistosomiasis, immunopathology and cytokine production in response to parasite eggs are uneven and strain dependent. CBA/J (CBA) mice develop severe hepatic granulomatous inflammation associated with prominent Th17 cell responses driven by dendritic cell (DC)-derived IL-1 beta and IL-23. Such Th17 cells fail to develop in low-pathology C57BL/6 (BL/6) mice, and the reasons for these strain-specific differences in APC reactivity to eggs remain unclear. We show by gene profiling that CBA DCs display an 18fold higher expression of the C-type lectin receptor CD209a, a murine homolog of human DC-specific ICAM-3-grabbing nonintegrin, compared with BL/6 DCs. Higher CD209a expression was observed in CBA splenic and granuloma APC subpopulations, but only DCs induced Th17 cell differentiation in response to schistosome eggs. Gene silencing in CBA DCs and overexpression in BL/6 DCs demonstrated that CD209a is essential for egg-elicited IL-1 beta and IL-23 production and subsequent Th17 cell development, which is associated with SRC, RAF-1, and ERK1/2 activation. These findings reveal a novel mechanism controlling the development of Th17 cell-mediated severe immunopathology in helminthic disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据