IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells.
IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+) Th17 cells.
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DOI：
10.1084/jem.20111453
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发表时间：
2012-08-27
期刊：
影响因子：
--
通讯作者：
Maloy KJ
中科院分区：
文献类型：
--
作者：
Coccia M;Harrison OJ;Schiering C;Asquith MJ;Becher B;Powrie F;Maloy KJ
IL-1β通过募集粒细胞、激活ILC、积累致病性T细胞和促进Th 17应答来促进慢性肠道炎症。尽管炎症性肠病（IBD）患者的肠道中存在非常高水平的白细胞介素（IL）-1β，但对IL-1β对肠道病理学的贡献知之甚少。在这里，我们使用了两种互补的慢性肠道炎症模型来解决IL-1β在驱动肠道先天性和适应性病理中的作用。我们发现，IL-1β通过增加粒细胞的募集和先天淋巴细胞（ILC）的积累和激活，促进肝螺杆菌引发的肠道炎症中的先天免疫病理学。使用T细胞转移结肠炎模型，我们证明了T细胞特异性IL-1受体（IL-1 R）信号在结肠中致病性CD 4 + T细胞的积累和存活中的关键作用。此外，我们表明IL-1β促进肠道中CD 4 + T细胞和ILC的Th 17应答，并且我们描述了IL-1β和IL-23信号之间的协同相互作用，这些信号维持肠道中的先天性和适应性炎症反应。这些数据确定了IL-1β促进肠道病理学的多种机制，并表明靶向IL-1β可能代表IBD中有用的治疗方法。
IL-1β promotes chronic intestinal inflammation through recruitment of granulocytes, activation of ILCs, accumulation of pathogenic T cells, and promotion of Th17 responses. Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intestinal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus–triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell–specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4+ T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4+ T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.
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影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
影响因子：
29.4
作者：
Asquith MJ;Boulard O;Powrie F;Maloy KJ
通讯作者：
Maloy KJ
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
DOI：
10.1073/pnas.0902745106
发表时间：
2009-04-28
影响因子：
11.1
作者：
Ben-Sasson, Shlomo Z.;Hu-Li, Jane;Paul, William E.
通讯作者：
Paul, William E.
DOI：
10.1179/096805102125000092
发表时间：
2002-01-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
Calkins, CM;Bensard, DD;McIntyre, RC
通讯作者：
McIntyre, RC