CD47 promotes peripheral T cell survival by preventing dendritic cell-mediated T cell necroptosis
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA(2023)
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(Delta T)) 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(Delta T) mice required expression of its receptor signal regulatory protein alpha 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(Delta T) mice. CD47 on T cells thus likely prevents their necroptotic cell death initiated by cDCs and thereby promotes T cell survival and function.
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Key words
T cell,dendritic cell,necroptosis,SIRP alpha,CD47
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