Tollip-induced down-regulation of MARCH1

Marie Claude Bourgeois-Daigneault, Abdul Mohammad Pezeshki, Tristan Galbas, Mathieu Houde, Martin Baril, Klaus Früh, Abdelaziz Amrani, Satoshi Ishido, Daniel Lamarre, Jacques Thibodeau

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

In addition to their classical antigen presenting functions, MHC class II molecules potentiate the TLR-triggered production of pro-inflammatory cytokines. Here, we have addressed the effect of Tollip and MARCH1 on the regulation of MHC II trafficking and TLR signaling. Our results show that MARCH1-deficient mice splenocytes are impaired in their capacity to produce pro-inflammatory cytokines in response to poly(I:C) and that TLR3 and MHC II molecules interact in the endocytic pathway. Knocking down Tollip expression in human CIITA+ HeLa cells increased expression of HLA-DR but reduced the proportion of MHC II molecules associated with the CLIP peptide. Truncation of the HLA-DR cytoplasmic tails abrogated the effect of Tollip on MHC class II expression. While overexpression of Tollip did not affect HLA-DR levels, it antagonized the function of co-transfected MARCH1. We found that Tollip strongly reduced MARCH1 protein levels and that the two molecules appear to compete for binding to MHC II molecules. Altogether, our results demonstrate that Tollip regulates MHC class II trafficking and that MARCH1 may represent a new Tollip target.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalResults in Immunology
Volume3
DOIs
StatePublished - Mar 14 2013

Keywords

  • Antigen presentation
  • MARCH1
  • MHC II
  • TLR3
  • Tollip

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Tollip-induced down-regulation of MARCH1'. Together they form a unique fingerprint.

  • Cite this

    Bourgeois-Daigneault, M. C., Pezeshki, A. M., Galbas, T., Houde, M., Baril, M., Früh, K., Amrani, A., Ishido, S., Lamarre, D., & Thibodeau, J. (2013). Tollip-induced down-regulation of MARCH1. Results in Immunology, 3, 17-25. https://doi.org/10.1016/j.rinim.2013.02.002