Dysregulated invertebrate tropomyosin-dectin-1 interaction confers susceptibility to allergic diseases.
Dysregulated invertebrate tropomyosin-dectin-1 interaction confers susceptibility to allergic diseases.
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DOI：
10.1126/sciimmunol.aam9841
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发表时间：
2018-02-23
影响因子：
24.8
通讯作者：
Wills-Karp M
中科院分区：
文献类型：
--
作者：
Gour N;Lajoie S;Smole U;White M;Hu D;Goddard P;Huntsman S;Eng C;Mak A;Oh S;Kim JH;Sharma A;Plante S;Salem IH;Resch Y;Xiao X;Yao N;Singh A;Vrtala S;Chakir J;Burchard EG;Lane AP;Wills-Karp M
The key factors underlying the development of allergic diseases—the propensity for a minority of individuals to develop dysfunctional responses to harmless environmental molecules—remain undefined. We report a pathway of immune counter-regulation that suppresses the development of aeroallergy and shrimp-induced anaphylaxis. In mice, signaling through epithelially expressed dectin-1 suppresses the development of type 2 immune responses through inhibition of interleukin-33 (IL-33) secretion and the subsequent recruitment of IL-13–producing innate lymphoid cells. Although this homeostatic pathway is functional in respiratory epithelial cells from healthy humans, it is dramatically impaired in epithelial cells from asthmatic and chronic rhinosinusitis patients, resulting in elevated IL-33 production. Moreover, we identify an association between a single-nucleotide polymorphism (SNP) in the dectin-1 gene loci and reduced pulmonary function in two cohorts of asthmatics. This intronic SNP is a predicted eQTL (expression quantitative trait locus) that is associated with reduced dectin-1 expression in human tissue. We identify invertebrate tropomyosin, a ubiquitous arthropod-derived molecule, as an immunobiologically relevant dectin-1 ligand that normally serves to restrain IL-33 release and dampen type 2 immunity in healthy individuals. However, invertebrate tropomyosin presented in the context of impaired dectin-1 function, as observed in allergic individuals, leads to unrestrained IL-33 secretion and skewing of immune responses toward type 2 immunity. Collectively, we uncover a previously unrecognized mechanism of protection against allergy to a conserved recognition element omnipresent in our environment.
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影响因子：
7.7
作者：
Chiba S;Ikushima H;Ueki H;Yanai H;Kimura Y;Hangai S;Nishio J;Negishi H;Tamura T;Saijo S;Iwakura Y;Taniguchi T
通讯作者：
Taniguchi T
DOI：
10.1084/jem.20100793
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barrett NA;Rahman OM;Fernandez JM;Parsons MW;Xing W;Austen KF;Kanaoka Y
通讯作者：
Kanaoka Y
影响因子：
15.9
作者：
Han, Hongwei;Thelen, Tennille D.;Ziegler, Steven F.
通讯作者：
Ziegler, Steven F.
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
2.9
作者：
BLACKWEL.J
通讯作者：
BLACKWEL.J