IL-23 is required for the development of severe egg-induced immunopathology in schistosomiasis and for lesional expression of IL-17
IL-23 is required for the development of severe egg-induced immunopathology in schistosomiasis and for lesional expression of IL-17
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DOI：
10.4049/jimmunol.180.4.2486
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发表时间：
2008-02-15
影响因子：
4.4
通讯作者：
Stadecker, Miguel J.
中科院分区：
文献类型：
--
作者：
Rutitzky, Laura I.;Bazzone, Lindsey;Stadecker, Miguel J.
感染曼氏血吸虫后，CD 4 T细胞介导的肝肉芽肿性和纤维化炎症对寄生虫卵的严重程度在人类和小鼠品系中差异很大。在小鼠中，天然的高病理学或通过在CFA（SEA/CFA）中伴随免疫接种卵裂球蛋白Ag（SEA）诱导的高病理学是由于未能包含净促炎细胞因子环境。我们先前证明，严重免疫病理学的诱导依赖于IL-12/IL-23共同p40亚基，并与IL-17的增加相关，因此暗示IL-23在发病机制中。我们现在表明，缺乏IL-23特异性亚基p19的小鼠在用SEA/CFA免疫后发展严重的免疫病理学中受损，这与肉芽肿中IL-17的显著下降有关，但与引流肠系膜淋巴结中的IL-17无关，并且与由IL-10的显著增加调节的SEA特异性IFN-γ应答的显著抑制有关。肉芽肿的特征是Gr-1（+）细胞募集显著减少和巨噬细胞交替活化。综上所述，这些结果表明，IL-23本身不是产生IL-17的T细胞所必需的，但对于严重的卵裂球诱导的免疫病理学的发展是必不可少的，并且它的缺乏不能用其他可能的补偿机制来克服。
In infection with the trematode helminth Schistosoma mansoni, the severity of CD4 T cell-mediated hepatic granulomatous and fibrosing inflammation against parasite eggs varies considerably in humans and among mouse strains. In mice, either the natural high pathology, or high pathology induced by concomitant immunization with schistosome egg Ags (SEA) in CFA (SEA/CFA), results from a failure to contain a net proinflammatory cytokine environment. We previously demonstrated that the induction of severe immunopathology was dependent on the IL-12/IL-23 common p40 subunit, and correlated with an increase in IL-17, thus implying IL-23 in the pathogenesis. We now show that mice lacking the IL-23-specific subunit p19 are impaired in developing severe immunopathology following immunization with SEA/CFA, which is associated with a marked drop of IL-17 in the granulomas, but not in the draining mesenteric lymph nodes, and with a markedly suppressed SEA-specific IFN-gamma response regulated by a striking increase in IL-10. The granulomas are characterized by a significant reduction in Gr-1(+) cell recruitment and by alternative macrophage activation. Taken together, these results demonstrate that IL-23 per se is not necessary for the generation of IL-17-producing T cells, but is essential for the development of severe schistosome egg-induced immunopathology, and its absence cannot be overcome with other possible compensatory mechanisms.