C3a is required for ILC2 function in allergic airway inflammation.
C3a is required for ILC2 function in allergic airway inflammation.
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DOI：
10.1038/s41385-018-0064-x
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发表时间：
2018-11
影响因子：
8
通讯作者：
Lajoie S
中科院分区：
文献类型：
--
作者：
Gour N;Smole U;Yong HM;Lewkowich IP;Yao N;Singh A;Gabrielson E;Wills-Karp M;Lajoie S
异常的2型反应是哮喘等过敏性疾病病理的基础，然而，我们对驱动它们的机制的理解仍然有限。最近的证据表明，先天免疫因子失调可使哮喘的发病机制永久化。在易感个体中，过敏原暴露会触发补体的激活，补体是先天免疫的一个主要分支，导致C3a过敏毒素的异常产生。C3和C3a已被证明对Th2应答的发展很重要，但值得注意的是，C3a调节2型免疫的机制相对未知。我们证明了C3a在驱动ilc2介导的炎症反应中对过敏原和IL-33的核心作用。我们的数据表明ILC2的招募依赖于c3a。此外，我们发现ILC2s直接响应C3a，通过特异性诱导IL-13和GM-CSF促进2型反应，同时抑制ILC2产生IL-10；2)增强它们在ILC-T细胞串扰中的抗原呈递能力。总之，我们发现了一种新的机制，C3a可以介导对空气过敏原暴露的异常2型反应，其中涉及两种主要先天免疫成分-补体和2组先天淋巴样细胞之间尚未被识别的串扰。
Aberrant type 2 responses underlie the pathologies in allergic diseases like asthma, yet, our understanding of the mechanisms that drive them remains limited. Recent evidence suggests that dysregulated innate immune factors can perpetuate asthma pathogenesis. In susceptible individuals, allergen exposure triggers the activation of complement, a major arm of innate immunity, leading to the aberrant generation of the C3a anaphylatoxin. C3 and C3a have been shown to be important for the development of Th2 responses, yet remarkably, the mechanisms by which C3a regulates type 2 immunity are relatively unknown. We demonstrate a central role for C3a in driving ILC2-mediated inflammation in response to allergen and IL-33. Our data suggests that ILC2 recruitment is C3a-dependent. Further, we show that ILC2s directly respond to C3a, promoting type 2 responses by specifically: 1) inducing IL-13 and GM-CSF, while inhibiting IL-10 production from ILC2; and 2) enhancing their antigen-presenting capability during ILC-T cell crosstalk. In summary, we identify a novel mechanism by which C3a can mediate aberrant type 2 responses to aeroallergen exposure, which involves a yet unrecognized crosstalk between two major innate immune components – complement and group 2 innate lymphoid cells.
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影响因子：
14.2
作者：
Jun, Sung Whan;Kim, Tae Hoon;Lee, Sang Hag
通讯作者：
Lee, Sang Hag
影响因子：
3
作者：
KAPP, A;WOKALEK, H;SCHOPF, E
通讯作者：
SCHOPF, E
DOI：
10.1016/j.jaci.2017.03.010
发表时间：
2018-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Karta MR;Rosenthal PS;Beppu A;Vuong CY;Miller M;Das S;Kurten RC;Doherty TA;Broide DH
通讯作者：
Broide DH
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1111/ajt.12405
发表时间：
2013-10
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Cravedi P;Leventhal J;Lakhani P;Ward SC;Donovan MJ;Heeger PS
通讯作者：
Heeger PS