Integrin CD11b negatively regulates Mincle-induced signaling pathway via the Lyn-Sirpα-Shp1 complex

Title
Integrin CD11b negatively regulates Mincle-induced signaling pathway via the Lyn-Sirpα-Shp1 complex
Authors
이욱빈장권일강지선김락균김영준
Issue Date
2018-02
Publisher
Experimental & molecular medicine
Citation
VOL 50, NO e439-17
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, SIRPα 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
http://pubs.kist.re.kr/handle/201004/69292
ISSN
1226-3613
Appears in Collections:
KIST Publication > Article
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