Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes.
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.
Thibodeau
Jacques
J
Département de Microbiologie et Immunologie, Université de Montréal, Montréal, QC, Canada. jacques.thibodeau@umontreal.ca
Bourgeois-Daigneault
Marie-Claude
MC
Huppé
Gabrielle
G
Tremblay
Jessy
J
Aumont
Angélique
A
Houde
Mathieu
M
Bartee
Eric
E
Brunet
Alexandre
A
Gauvreau
Marie-Elaine
ME
de Gassart
Aude
A
Gatti
Evelina
E
Baril
Martin
M
Cloutier
Maryse
M
Bontron
Séverine
S
Früh
Klaus
K
Lamarre
Daniel
D
Steimle
Viktor
V
D051940:B7-2 Antigen / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006681:HLA-D Antigens / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*; D054875:Ubiquitination / Q000276:immunology
D051940:B7-2 Antigen; C497964:CD86 protein, human; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; C083728:MHC class II transactivator protein; D008565:Membrane Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D016753:Interleukin-10; D007371:Interferon-gamma; C528121:MARCHF1 protein, human; C568898:MARCHF8 protein, human; D044767:Ubiquitin-Protein Ligases