Interactions between CD47 and thrombospondin reduce inflammation.
CD47 on the surface of T cells was shown in vitro to mediate either T cell activation or, in the presence of high amounts of thrombospondin (TSP), T cell apoptosis. We report here that CD47-deficient mice, as well as TSP-1 or TSP-2-deficient mice, sustain oxazolone-induced inflammation for more than four days, whereas wild-type mice reduce the inflammation within 48 h. We observe that prolonged inflammation in CD47-, TSP-1-, or TSP-2-deficient mice is accompanied by a local deficiency of T cell apoptosis. Finally, we show that upon activation normal T cells increase the expression of the proapoptotic Bcl-2 family member BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) and undergo CD47-mediated apoptosis. This finding is consistent with our previous demonstration of a physical interaction between BNIP3 and CD47 that inhibits BNIP3 degradation by the proteasome, sensitizing T cells to CD47-induced apoptosis. Overall, these results reveal an important role in vivo for this new CD47/BNIP3 pathway in limiting inflammation by controlling the number of activated T cells.
Lamy
Laurence
L
INSERM Unit 576, Hospitalier de l'Université de Nice, University of Nice-Sophia Antipolis, Hôpital de l'Archet I, 151 rue Saint Antoine de Ginestière, Nice, France.
Foussat
Arnaud
A
Brown
Eric J
EJ
Bornstein
Paul
P
Ticchioni
Michel
M
Bernard
Alain
A
D000818:Animals; D017209:Apoptosis; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism*; D003872:Dermatitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010081:Oxazolone / Q000633:toxicity; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D019700:Thrombospondin 1 / Q000172:deficiency* / Q000235:genetics; D019699:Thrombospondins / Q000172:deficiency* / Q000235:genetics; D000099262:Thrombospondin 2
D051928:CD47 Antigen; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010081:Oxazolone; D046988:Proteasome Endopeptidase Complex; D019700:Thrombospondin 1; D019699:Thrombospondins; D000099262:Thrombospondin 2; C508686:BNip3 protein, mouse