CD47 promotes peripheral T cell survival by preventing dendritic cell-mediated T cell necroptosis

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2304943120. doi: 10.1073/pnas.2304943120. Epub 2023 Aug 7.

Abstract

Conventional dendritic cells (cDCs) are required for peripheral T cell homeostasis in lymphoid organs, but the molecular mechanism underlying this requirement has remained unclear. We here show that T cell-specific CD47-deficient (Cd47 ΔT) mice have a markedly reduced number of T cells in peripheral tissues. Direct interaction of CD47-deficient T cells with cDCs resulted in activation of the latter cells, which in turn induced necroptosis of the former cells. The deficiency and cell death of T cells in Cd47 ΔT mice required expression of its receptor signal regulatory protein α on cDCs. The development of CD4+ T helper cell-dependent contact hypersensitivity and inhibition of tumor growth by cytotoxic CD8+ T cells were both markedly impaired in Cd47 ΔT mice. CD47 on T cells thus likely prevents their necroptotic cell death initiated by cDCs and thereby promotes T cell survival and function.

Keywords: CD47; SIRPα; T cell; dendritic cell; necroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD47 Antigen* / genetics
  • CD47 Antigen* / metabolism
  • CD8-Positive T-Lymphocytes* / metabolism
  • Cell Survival
  • Dendritic Cells / metabolism
  • Mice
  • Necroptosis
  • Receptors, Immunologic / metabolism

Substances

  • CD47 Antigen
  • Receptors, Immunologic
  • Cd47 protein, mouse