Integrin CD11b negatively regulates mincle-induced signaling via the lyn–SIRPα–SHP1 complex

Quanri Zhang, Wook Bin Lee, Ji Seon Kang, Lark Kyun Kim, Young Joon Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article numbere439
JournalExperimental and Molecular Medicine
Volume50
Issue number2
DOIs
Publication statusPublished - 2018 Feb 2

Fingerprint

C-Type Lectins
Integrins
Macrophages
Mycobacterium Infections
Mycobacterium
Cord Factors
Macrophage Activation
Immune system
Immune System
Anti-Inflammatory Agents
Modulators
Inflammation
Tuning
Chemical activation
Tissue
Infection

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

@article{d58321bc01cb4d3398927c712b06c2a3,
title = "Integrin CD11b negatively regulates mincle-induced signaling via the lyn–SIRPα–SHP1 complex",
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.",
author = "Quanri Zhang and Lee, {Wook Bin} and Kang, {Ji Seon} and Kim, {Lark Kyun} and Kim, {Young Joon}",
year = "2018",
month = "2",
day = "2",
doi = "10.1038/emm.2017.256",
language = "English",
volume = "50",
journal = "Experimental and Molecular Medicine",
issn = "1226-3613",
publisher = "Korean Society of Med. Biochemistry and Mol. Biology",
number = "2",

}

Integrin CD11b negatively regulates mincle-induced signaling via the lyn–SIRPα–SHP1 complex. / Zhang, Quanri; Lee, Wook Bin; Kang, Ji Seon; Kim, Lark Kyun; Kim, Young Joon.

In: Experimental and Molecular Medicine, Vol. 50, No. 2, e439, 02.02.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Integrin CD11b negatively regulates mincle-induced signaling via the lyn–SIRPα–SHP1 complex

AU - Zhang, Quanri

AU - Lee, Wook Bin

AU - Kang, Ji Seon

AU - Kim, Lark Kyun

AU - Kim, Young Joon

PY - 2018/2/2

Y1 - 2018/2/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85054743744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054743744&partnerID=8YFLogxK

U2 - 10.1038/emm.2017.256

DO - 10.1038/emm.2017.256

M3 - Article

C2 - 29400702

AN - SCOPUS:85054743744

VL - 50

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

SN - 1226-3613

IS - 2

M1 - e439

ER -