Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 9, Pages 5916-5926Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.9.5916
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Funding
- Medical Research Council [MC_U117527252] Funding Source: researchfish
- Medical Research Council [MC_U117527252] Funding Source: Medline
- NCI NIH HHS [R01 CA 94037] Funding Source: Medline
- NHLBI NIH HHS [T32 HL 072739] Funding Source: Medline
- MRC [MC_U117527252] Funding Source: UKRI
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Lymphocyte activation gene-3 (LAG-3) is a CD4-related transmembrane protein expressed by regulatory T cells that binds MHC H on APCs. It is shown in this study that during Treg:DC interactions, LAG-3 engagement with MHC class II inhibits DC activation. MHC H cross-linking by agonistic Abs induces an ITAM-mediated inhibitory signaling pathway, involving Fc gamma R gamma and ERK-mediated recruitment of SHP-1 that suppresses dendritic cell maturation and inummostimulatory capacity. These data reveal a novel ITAM-mediated inhibitory signaling pathway in DCs triggered by MHC H engagement of LAG-3, providing a molecular mechanism in which regulatory T cells may suppress via modulating DC function.
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