Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II

B Liang, C Workman, J Lee, C Chew… - The Journal of …, 2008 - journals.aai.org
B Liang, C Workman, J Lee, C Chew, BM Dale, L Colonna, M Flores, N Li, E Schweighoffer…
The Journal of Immunology, 2008journals.aai.org
Abstract Lymphocyte activation gene-3 (LAG-3) is a CD4-related transmembrane protein
expressed by regulatory T cells that binds MHC II on APCs. It is shown in this study that
during Treg: DC interactions, LAG-3 engagement with MHC class II inhibits DC activation.
MHC II cross-linking by agonistic Abs induces an ITAM-mediated inhibitory signaling
pathway, involving FcγRγ and ERK-mediated recruitment of SHP-1 that suppresses dendritic
cell maturation and immunostimulatory capacity. These data reveal a novel ITAM-mediated …
Abstract
Lymphocyte activation gene-3 (LAG-3) is a CD4-related transmembrane protein expressed by regulatory T cells that binds MHC II on APCs. It is shown in this study that during Treg: DC interactions, LAG-3 engagement with MHC class II inhibits DC activation. MHC II cross-linking by agonistic Abs induces an ITAM-mediated inhibitory signaling pathway, involving FcγRγ and ERK-mediated recruitment of SHP-1 that suppresses dendritic cell maturation and immunostimulatory capacity. These data reveal a novel ITAM-mediated inhibitory signaling pathway in DCs triggered by MHC II engagement of LAG-3, providing a molecular mechanism in which regulatory T cells may suppress via modulating DC function.
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