Open AccessRegulatory T Cells Inhibit Dendritic Cells by Lymphocyte Activation Gene-3 Engagement of MHC Class II
Author(s) -
Bitao Liang,
Craig D. Workman,
Janine Lee,
Claude Chew,
Benjamin M. Dale,
Lucrezia Colonna,
Marcella Flores,
Nianyu Li,
Edina Schweighoffer,
Steven M. Greenberg,
Victor L. J. Tybulewicz,
Dario A.A. Vignali,
Raphael Clynes
Publication year - 2008
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.180.9.5916
Subject(s) - microbiology and biotechnology , mhc class ii , mhc class i , transmembrane protein , dendritic cell , t cell , major histocompatibility complex , biology , chemistry , immune system , immunology , receptor , genetics
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 FcgammaRgamma 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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