Stromal Cell Induction of Regulatory Dendritic Cells

Benjamin M. J. Owens,Paul M. Kaye

doi:10.3389/fimmu.2012.00262

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.

Highlights

Dendritic cells (DCs) lie at the interface of innate and adaptive immunity, playing a critical role in the initiation of effective T cell-mediated immune responses
A body of literature has developed that suggests that DCs, as well as many other myeloid cell populations, are capable of exerting “regulatory” effects on T cell responses
Recent data strongly support the concept that CD11chi DCs (cDCs) belong to a distinct immune cell lineage (Meredith et al, 2012; Satpathy et al, 2012)

Summary

Stromal cell induction of regulatory dendritic cells

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. A body of literature has developed that suggests that DCs, as well as many other myeloid cell populations, are capable of exerting “regulatory” effects on T cell responses. 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 focus on the contribution of non-hematopoietic stromal cells to their generation within specific tissue microenvironments.

INTRODUCTION

Stromal cells and regulatory DCs