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Significance Conventional dendritic cells (cDCs), cDC1s and cDC2s, are hematopoietic cells that play central roles in mounting T cell responses. It is important for host protection that cDCs are continuously replenished by bone marrow precursors. cDC1s and cDC2s rely on the cytokine FLT3L, and, because both subsets mount different types of immune responses, their relative abundance must be regulated and balanced. In this work, we demonstrated that cDC2s produced their own FLT3L and utilized the transmembrane metalloproteinase ADAM10 to shed membrane-bound FLT3L into soluble forms. This process was crucial for cDC2s to develop and survive in the spleen. These findings likely represent cell-autonomous developmental and survival processes that enable cDC2s to preferentially gain access to FLT3L.

Cell-autonomous FLT3L shedding via ADAM10 mediates conventional dendritic cell development in mouse spleen