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

Thibodeau J, Bourgeois-Daigneault MC, Huppé G, Tremblay J, Aumont A, Houde M, Bartee E, Brunet A, Gauvreau ME, de Gassart A, Gatti E, Baril M, Cloutier M, Bontron S, Früh K, Lamarre D, Steimle V

Département de Microbiologie et Immunologie, Université de Montréal, Montréal, QC, Canada. jacques.thibodeau@umontreal.ca

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 down-regulation 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.

Eur. J. Immunol. 2008;38(5):1225-30.

Pubmed ID: 18389477

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