Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs

Signal regulatory protein α ( SIRP α), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells ( DC s) or macrophages, mediates cell–cell signaling. In the immune system, SIRP α is thought to be important for homeostasis of DC s, but it remains unclear whether SIRP α intrinsic to DC s is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRP α was specifically ablated in CD 11c + DC s ( Sirpa Δ DC ). Sirpa Δ DC mice manifested a marked reduction of CD 4 + CD 8α – conventional DC s ( cDC s) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDC s in Sirpa Δ DC mice was comparable to that apparent with the mice, in which SIRP α was systemically ablated. Expression of SIRP α in DC s was well correlated with that of either endothelial cell‐selective adhesion molecule ( ESAM ) or Epstein–Barr virus‐induced molecule 2 ( EBI 2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM + or EBI 2 + cDC s were markedly reduced in the spleen of Sirpa Δ DC mice. Thus, our results suggest that SIRP α intrinsic to CD 11c + DC s is essential for homeostasis of cDC s in the secondary lymphoid organs and skin.