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Integrin CD11b negatively regulates Mincle-induced signaling via the Lyn-SIRPalpha-SHP1 complex

Authors
 Quanri Zhang  ;  Wook-Bin Lee  ;  Ji-Seon Kang  ;  Lark Kyun Kim  ;  Young-Joon Kim 
Citation
 Experimental and Molecular Medicine, Vol.50(2) : e439, 2018 
Journal Title
 Experimental and Molecular Medicine 
ISSN
 1226-3613 
Issue Date
2018
Abstract
During mycobacteria infection, anti-inflammatory responses allow the host to avoid tissue damage caused by overactivation of the immune system; however, little is known about the negative modulators that specifically control mycobacteria-induced immune responses. Here we demonstrate that integrin CD11b is a critical negative regulator of mycobacteria cord factor-induced macrophage-inducible C-type lectin (Mincle) signaling. CD11b deficiency resulted in hyperinflammation following mycobacterial infection. Activation of Mincle by mycobacterial components turns on not only the Syk signaling pathway but also CD11b signaling and induces formation of a Mincle-CD11b signaling complex. The activated CD11b recruits Lyn, SIRPalpha and SHP1, which dephosphorylate Syk to inhibit Mincle-mediated inflammation. Furthermore, the Lyn activator MLR1023 effectively suppressed Mincle signaling, indicating the possibility of Lyn-mediated control of inflammatory responses. These results describe a new role for CD11b in fine-tuning the immune response against mycobacterium infection.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162364
Files in This Item:
T201801446.pdf Download
DOI
10.1038/emm.2017.256
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
김락균(Kim, Lark Kyun) ORCID logo https://orcid.org/0000-0001-5983-4470
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