Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II.
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.
Liang
Bitao
B
Departments of Microbiology, Pharmacology and Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Workman
Craig
C
Lee
Janine
J
Chew
Claude
C
Dale
Benjamin M
BM
Colonna
Lucrezia
L
Flores
Marcella
M
Li
Nianyu
N
Schweighoffer
Edina
E
Greenberg
Steven
S
Tybulewicz
Victor
V
Vignali
Dario
D
Clynes
Raphael
R
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D007152:Immunologic Capping / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000093322:Lymphocyte Activation Gene 3 Protein
D000906:Antibodies; D015703:Antigens, CD; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D017452:Receptors, IgG; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse