Mincle suppresses Toll-like receptor 4 activation.

Journal Article (Journal Article)

Regulation of Toll-like receptor responses is critical for limiting tissue injury and autoimmunity in both sepsis and sterile inflammation. We found that Mincle, a C-type lectin receptor, regulates proinflammatory Toll-like receptor 4 signaling. Specifically, Mincle ligation diminishes Toll-like receptor 4-mediated inflammation, whereas Mincle deletion or knockdown results in marked hyperresponsiveness to lipopolysaccharide in vitro, as well as overwhelming lipopolysaccharide-mediated inflammation in vivo. Mechanistically, Mincle deletion does not up-regulate Toll-like receptor 4 expression or reduce interleukin 10 production after Toll-like receptor 4 ligation; however, Mincle deletion decreases production of the p38 mitogen-activated protein kinase-dependent inhibitory intermediate suppressor of cytokine signaling 1, A20, and ABIN3 and increases expression of the Toll-like receptor 4 coreceptor CD14. Blockade of CD14 mitigates the increased sensitivity of Mincle(-/-) leukocytes to Toll-like receptor 4 ligation. Collectively, we describe a major role for Mincle in suppressing Toll-like receptor 4 responses and implicate its importance in nonmycobacterial models of inflammation.

Full Text

Duke Authors

Cited Authors

  • Greco, SH; Mahmood, SK; Vahle, A-K; Ochi, A; Batel, J; Deutsch, M; Barilla, R; Seifert, L; Pachter, HL; Daley, D; Torres-Hernandez, A; Hundeyin, M; Mani, VR; Miller, G

Published Date

  • July 2016

Published In

Volume / Issue

  • 100 / 1

Start / End Page

  • 185 - 194

PubMed ID

  • 26747838

Pubmed Central ID

  • 26747838

Electronic International Standard Serial Number (EISSN)

  • 1938-3673

International Standard Serial Number (ISSN)

  • 0741-5400

Digital Object Identifier (DOI)

  • 10.1189/jlb.3a0515-185r

Language

  • eng