Infection of avian influenza virus, especially the highly pathogenic strain H5N1, is a serious threat to public health worldwide. H5N1 infection causes severe fatal respiratory disease and excessive levels of inflammation. Previous studies have demonstrated that both transforming growth factor-beta 1 (TGF-β1) and the integrin CD103 play protective roles against influenza virus infection. It is therefore critical to identify the key signaling proteins that regulate the cross-talk between TGF-β1 and integrins during H5N1 virus infection.
Professor WANG Hongyan’s lab from the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, has identified that the adaptor protein ADAP (adhesion and degranulation promoting adaptor protein) regulates the TGF-β1-integrin crosstalk. In this study, researchers demonstrated that ADAP formed a complex with TRAF6 and TAK1 to activate SMAD3 in CD8+ T cells, which increased TGF-β1 production in an autocrine manner. Moreover, TGF-β1-induced CD103 expression was also dependent on ADAP, TRAF6, TAK1 and SMAD3. Importantly, in response to H5N1 virus infection, ADAP deficient mice decreases TGF-β1 production and surface CD103 expression in lung infiltrating CD8+ T cells with the enhanced mortality when compared with the wild-type control mice.
This work entitled “The Immune Adaptor ADAP Regulates Reciprocal TGF-β1-Integrin Crosstalk to Protect from Influenza Virus Infection” was published online in PLoS Pathogens on April 24, 2015. The key message is simplified as the cartoon “3 little pigs (ADAP, TGF-β1 and CD103) try to protect from the bad wolf’s (H5N1) cytokine storm.
This work was supported by grants from the Ministry of Science and Technology of China, National Natural Science Foundation of China, the Program of the Chinese Academy of Sciences. It was collaborated with Prof. CHEN Hualan from Harbin Veterinary Research Institute, CAAS.
AUTHOR CONTACT:
WANG Hongyan
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai 200031, China
Phone: 021-54921086
E-mail: hongyanwang@sibcb.ac.cn
(Image provided by Prof. WANG Hongyan`s group)
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