title: Mincle suppresses Toll-like receptor 4 activation.
abstract: 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.
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Greco
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Syed Kashif
authors.initials: SK
authors.lastname: Mahmood
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Anne-Kristin
authors.initials: AK
authors.lastname: Vahle
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ochi
authors.affiliation: Department of Cell Biology, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Batel
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Deutsch
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Rocky
authors.initials: R
authors.lastname: Barilla
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Lena
authors.initials: L
authors.lastname: Seifert
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: H Leon
authors.initials: HL
authors.lastname: Pachter
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Donnele
authors.initials: D
authors.lastname: Daley
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Torres-Hernandez
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Mautin
authors.initials: M
authors.lastname: Hundeyin
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and.
authors.forename: Vishnu R
authors.initials: VR
authors.lastname: Mani
authors.affiliation: Department of Surgery, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA; and Department of Cell Biology, S. Arthur Localio Laboratory, New York University School of Medicine, New York, NY, USA george.miller@nyumc.org.
authors.forename: George
authors.initials: G
authors.lastname: Miller
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type / Q000172:deficiency* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C113583:Clecsf8 protein, mouse; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: C-type lectin receptor; inflammation; sepsis