TY - JOUR
T1 - Tollip-induced down-regulation of MARCH1
AU - Bourgeois-Daigneault, Marie Claude
AU - Pezeshki, Abdul Mohammad
AU - Galbas, Tristan
AU - Houde, Mathieu
AU - Baril, Martin
AU - Früh, Klaus
AU - Amrani, Abdelaziz
AU - Ishido, Satoshi
AU - Lamarre, Daniel
AU - Thibodeau, Jacques
N1 - Funding Information:
We thank Dr. Gerardo Ferbeyre (Université de Montréal, Montreal, QC, Canada) and Dr. Liwu Li (Virginia Polytechnic Institute and State University, Virginia, USA) for providing the GFP-SOCS1 and GFP-Tollip, respectively. MCBD was supported by a fellowship from the Cole foundation. This project was supported by grants from the Roche Organ Transplantation Research Foundation/Juvenile Diabetes Research Foundation joint initiative (Project #665990157) to JT and AA and by the Canadian Institutes for Health Research (CIHR; Grant # 93592 ) to JT.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Antigen presentation
KW - MARCH1
KW - MHC II
KW - TLR3
KW - Tollip
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U2 - 10.1016/j.rinim.2013.02.002
DO - 10.1016/j.rinim.2013.02.002
M3 - Article
AN - SCOPUS:84874804050
SN - 2211-2839
VL - 3
SP - 17
EP - 25
JO - Results in Immunology
JF - Results in Immunology
ER -