Abstract
Dendritic cells (DCs) are specialized antigen presenting cells of bone marrow origin that can exist in tissues in either an immature or mature state. DCs have a myriad of roles in immunity and tolerance induction, but are perhaps best known for their role in the activation and differentiation of naïve T cells at the onset of an acquired immune response. Over the past decade, a body of literature has developed that suggests that DCs, as well as many other myeloid cell populations, are also capable of exerting "regulatory" effects on T cell responses. However, relatively little is known regarding the mechanisms by which such regulatory myeloid cells arise in vivo. In this mini-review, we first define the characteristics of "regulatory" DCs (rDCs) and then focus on the contribution of non-hematopoietic stromal cells to their generation within specific tissue microenvironments. We also highlight areas of research that warrant future attention, arguing for a focusing of efforts toward a better understanding of the features of stromal cell populations that enable the induction of rDCs. Finally, we discuss how an understanding of stromal cell-myeloid cell interactions may lead to new therapeutic strategies for cancer, autoimmunity, and infectious disease.