IL-33 induced Ag-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4
IL-33 induced Ag-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4
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DOI：
10.4049/jimmunol.181.11.8170
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发表时间：
2008-12
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通讯作者：
M. Kurowska-Stolarska;P. Kewin;G. Murphy;R. C. Russo;B. Stolarski;Cristiana Couto Garcia;M. Komai‐Koma;N. Pitman;Yubin Li;W. Niedbala;Andrew N. J. McKenzie;Mauro M Teixeira;Fooyew Liew;Damo Xu
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作者：
M. Kurowska-Stolarska;P. Kewin;G. Murphy;R. C. Russo;B. Stolarski;Cristiana Couto Garcia;M. Komai‐Koma;N. Pitman;Yubin Li;W. Niedbala;Andrew N. J. McKenzie;Mauro M Teixeira;Fooyew Liew;Damo Xu
2型细胞因子（IL-4、IL-5和IL-13）在蠕虫感染和变应性疾病中起关键作用。产生2型细胞因子的CD 4（+）T细胞可以通过IL-4依赖性和非依赖性途径产生。虽然IL-4依赖性途径是有据可查的，但驱动IL-4非依赖性Th 2细胞分化的因素仍然不清楚。我们在此报道，新的细胞因子IL-33在Ag存在的情况下，将鼠和人的幼稚CD 4（+）T细胞极化成主要产生IL-5而不产生IL-4的T细胞群体。这种极化需要IL-1 R相关分子和MyD 88，而不需要IL-4或STAT 6。IL-33诱导的T细胞分化也依赖于MAPK和NF-κ B的磷酸化，而不是GATA 3或T-bet的诱导。在体内，ST 2（-/-）小鼠在哮喘小鼠模型中产生了减弱的气道炎症和IL-5产生。相反，IL-33给药诱导产生IL-5的T细胞，并加剧野生型和IL-4（-/-）小鼠中过敏原诱导的气道炎症。最后，IL-33极化的IL-5（+）IL-4（-）T细胞的过继转移在初始IL-4（-/-）小鼠中触发气道炎症。因此，我们在这里证明，在Ag的存在下，IL-33诱导产生IL-5的T细胞，并促进气道炎症独立于IL-4。
Type 2 cytokines (IL-4, IL-5, and IL-13) play a pivotal role in helminthic infection and allergic disorders. CD4(+) T cells which produce type 2 cytokines can be generated via IL-4-dependent and -independent pathways. Although the IL-4-dependent pathway is well documented, factors that drive IL-4-independent Th2 cell differentiation remain obscure. We report here that the new cytokine IL-33, in the presence of Ag, polarizes murine and human naive CD4(+) T cells into a population of T cells which produce mainly IL-5 but not IL-4. This polarization requires IL-1R-related molecule and MyD88 but not IL-4 or STAT6. The IL-33-induced T cell differentiation is also dependent on the phosphorylation of MAPKs and NF-kappaB but not the induction of GATA3 or T-bet. In vivo, ST2(-/-) mice developed attenuated airway inflammation and IL-5 production in a murine model of asthma. Conversely, IL-33 administration induced the IL-5-producing T cells and exacerbated allergen-induced airway inflammation in wild-type as well as IL-4(-/-) mice. Finally, adoptive transfer of IL-33-polarized IL-5(+)IL-4(-)T cells triggered airway inflammation in naive IL-4(-/-) mice. Thus, we demonstrate here that, in the presence of Ag, IL-33 induces IL-5-producing T cells and promotes airway inflammation independent of IL-4.