Resident CD141 (BDCA3) ⁺ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation

Abstract

Human skin-resident IL-10 ⁺ regulatory dendritic cells induce T reg cells that suppress allogeneic skin graft inflammation.

Abstract

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141 ⁺ DDCs). CD141 ⁺ DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D ₃ (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141 ⁺ DDCs from human blood DCs. These CD141 ⁺ DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141 ⁺ DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141 ⁺ DDC-like cells have potential clinical use for their capacity to induce immune tolerance.