Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes

Jacques Thibodeau, Marie Claude Bourgeois-Daigneault, Gabrielle Huppé, Jessy Tremblay, Angélique Aumont, Mathieu Houde, Eric Bartee, Alexandre Brunet, Marie Elaine Gauvreau, Aude de Gassart, Evelina Gatti, Martin Baril, Maryse Cloutier, Séverine Bontron, Klaus Früh, Daniel Lamarre, Viktor Steimle

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

IL-10 is a potent anti-inflammatory cytokine interfering with antigen presentation by inducing the intracellular sequestration of MHC class II (MHC-II) molecules. Here we studied the contribution of membrane-associated RING-CH (MARCH) ubiquitin ligase family members to the IL-10-induced down-regulation of MHC-II molecules. We found that MARCH1 and MARCH8 proteins are the most potent family members for the downregulation of MHC-II surface expression in transfected cells, but only MARCH1 mRNA expression is strongly induced by IL-10 in human primary monocytes.We detected mono-and poly-ubiquitinated forms of MHC-II molecules both in IL-10-treated monocytes and in cells transfected with MARCH1. We also show direct interaction between MHC-II and MARCH1 molecules in co-immunoprecipitation assays. Finally, we found that siRNA-mediated knockdown of MARCH1 reverses IL-10-induced MHC-II down-regulation in primary monocytes. Thus, the immunosuppressive effect of IL-10 on antigen presentation is mediated through induced expression of MARCH1.

Original languageEnglish (US)
Pages (from-to)1225-1230
Number of pages6
JournalEuropean Journal of Immunology
Volume38
Issue number5
DOIs
StatePublished - May 1 2008

Keywords

  • Antigen-presenting cells
  • Cytokines
  • Immune regulation
  • Inflammation
  • MHC

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Thibodeau, J., Bourgeois-Daigneault, M. C., Huppé, G., Tremblay, J., Aumont, A., Houde, M., Bartee, E., Brunet, A., Gauvreau, M. E., de Gassart, A., Gatti, E., Baril, M., Cloutier, M., Bontron, S., Früh, K., Lamarre, D., & Steimle, V. (2008). Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes. European Journal of Immunology, 38(5), 1225-1230. https://doi.org/10.1002/eji.200737902