Mincle suppresses toll-like receptor 4 activation

Stephanie H. Greco, Syed Kashif Mahmood, Anne Kristin Vahle, Atsuo Ochi, Jennifer Batel, Michael Deutsch, Rocky Barilla, Lena Seifert, H. Leon Pachter, Donnele Daley, Alejandro Torres-Hernandez, Mautin Hundeyin, Vishnu R. Mani, George Miller

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 upregulate 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.

Original languageEnglish (US)
Pages (from-to)185-194
Number of pages10
JournalJournal of Leukocyte Biology
Volume100
Issue number1
DOIs
StatePublished - Jul 1 2016

Fingerprint

Toll-Like Receptor 4
Inflammation
Ligation
Toll-Like Receptors
Lipopolysaccharides
C-Type Lectins
p38 Mitogen-Activated Protein Kinases
Autoimmunity
Interleukin-10
Sepsis
Leukocytes
Up-Regulation
Cytokines
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Greco, S. H., Mahmood, S. K., Vahle, A. K., Ochi, A., Batel, J., Deutsch, M., ... Miller, G. (2016). Mincle suppresses toll-like receptor 4 activation. Journal of Leukocyte Biology, 100(1), 185-194. https://doi.org/10.1189/jlb.3A0515-185R
Greco, Stephanie H. ; Mahmood, Syed Kashif ; Vahle, Anne Kristin ; Ochi, Atsuo ; Batel, Jennifer ; Deutsch, Michael ; Barilla, Rocky ; Seifert, Lena ; Leon Pachter, H. ; Daley, Donnele ; Torres-Hernandez, Alejandro ; Hundeyin, Mautin ; Mani, Vishnu R. ; Miller, George. / Mincle suppresses toll-like receptor 4 activation. In: Journal of Leukocyte Biology. 2016 ; Vol. 100, No. 1. pp. 185-194.
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Greco, SH, Mahmood, SK, Vahle, AK, Ochi, A, Batel, J, Deutsch, M, Barilla, R, Seifert, L, Leon Pachter, H, Daley, D, Torres-Hernandez, A, Hundeyin, M, Mani, VR & Miller, G 2016, 'Mincle suppresses toll-like receptor 4 activation', Journal of Leukocyte Biology, vol. 100, no. 1, pp. 185-194. https://doi.org/10.1189/jlb.3A0515-185R

Mincle suppresses toll-like receptor 4 activation. / Greco, Stephanie H.; Mahmood, Syed Kashif; Vahle, Anne Kristin; Ochi, Atsuo; Batel, Jennifer; Deutsch, Michael; Barilla, Rocky; Seifert, Lena; Leon Pachter, H.; Daley, Donnele; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Miller, George.

In: Journal of Leukocyte Biology, Vol. 100, No. 1, 01.07.2016, p. 185-194.

Research output: Contribution to journalArticle

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AU - Greco, Stephanie H.

AU - Mahmood, Syed Kashif

AU - Vahle, Anne Kristin

AU - Ochi, Atsuo

AU - Batel, Jennifer

AU - Deutsch, Michael

AU - Barilla, Rocky

AU - Seifert, Lena

AU - Leon Pachter, H.

AU - Daley, Donnele

AU - Torres-Hernandez, Alejandro

AU - Hundeyin, Mautin

AU - Mani, Vishnu R.

AU - Miller, George

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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 upregulate 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.

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Greco SH, Mahmood SK, Vahle AK, Ochi A, Batel J, Deutsch M et al. Mincle suppresses toll-like receptor 4 activation. Journal of Leukocyte Biology. 2016 Jul 1;100(1):185-194. https://doi.org/10.1189/jlb.3A0515-185R