Interactions between CD47 and thrombospondin reduce inflammation.

Therapeutic Approaches

Abstract

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.

Authors

Lamy, Laurence; Foussat, Arnaud; Brown, Eric J; Bornstein, Paul; Ticchioni, Michel; Bernard, Alain;

Keywords

  • Animals
  • Antigens, CD47/ genetics
  • Antigens, CD47/ metabolism
  • Apoptosis
  • Dermatitis/ genetics
  • Dermatitis/ immunology
  • Dermatitis/ pathology
  • Inflammation/ chemically induced
  • Inflammation/ immunology
  • Inflammation/ pathology
  • Membrane Proteins/ metabolism
  • Mice
  • Mice, Mutant Strains
  • Mitochondrial Proteins/ metabolism
  • Oxazolone/ toxicity
  • Proteasome Endopeptidase Complex/ metabolism
  • T-Lymphocytes/ immunology
  • Thrombospondin 1/ deficiency
  • Thrombospondin 1/ genetics
  • Thrombospondins/ deficiency
  • Thrombospondins/ genetics

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