Sustained Rap1 activation in autoantigen-specific T lymphocytes attenuates experimental autoimmune encephalomyelitis.
Altered Ras superfamily guanine nucleotide triphosphatase signaling may contribute to the activation of autoreactive T cells in diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here, we show that transgenic expression of activated Rap1, a Ras-related protein which is protective in murine arthritis, in both wildtype (WT) and 2D2 mice, enhances autoreactive T cell activation by myelin oligodendrocyte glycoprotein peptide in vitro and in vivo. However, RapV12 reduces the number of autoreactive T cells in both WT and 2D2 mice, and increases murine survival in experimental autoimmune encephalitis, suggesting Rap1 activation restricts autoimmune T cell-mediated pathology through enhancing tolerance.
Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Gabriela Franco
GF
Salinas
Sarah
S
Krausz
Wendy
W
Dontje
Brian D
BD
Evavold
Paul P
PP
Tak
Dominique L
DL
Baeten
Kris A
KA
Reedquist
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D020827:rap1 GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D020827:rap1 GTP-Binding Proteins