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KMID : 0620920180500020004
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Experimental & Molecular Medicine
2018 Volume.50 No. 2 p.4 ~ p.4
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Integrin CD11b negatively regulates Mincle-induced signaling via the Lyn?SIRPα?SHP1 complex
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Zhang Quanri
Lee Wook-Bin
Kang Ji-Seon
Kim Lark-Kyun
Kim Young-Joon
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Abstract
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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.
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KEYWORD
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Acute inflammation, Extracellular signalling molecules, Pattern recognition receptors
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