TGF-beta1 regulation of dendritic cells

Abstract

Dendritic cells (DCs) represent antigen-presenting cell (APC) populations in lymphoid and nonlymphoid organs which are considered to play key roles in the initiation of antigen-specific T-cell proliferation. According to current knowledge, the net outcome of T-cell immune responses seems to be significantly influenced by the activation stage of antigen-presenting DCs. Several studies have shown that transforming growth factor-beta 1 (TGF-beta1) inhibits in vitro activation and maturation of DCs. TGF-beta1 inhibits upregulation of critical T-cell costimulatory molecules on the surface of DCs and reduces the antigen-presenting capacity of DCs. Thus, in addition to direct inhibitory effects of TGF-beta1 on effector T lymphocytes, inhibitory effects of TGF-beta1 at the level of APCs may critically contribute to previously characterized immunosuppressive effects of TGF-beta1. In contrast to these negative regulatory effects of TGF-beta1 on function and maturation of lymphoid tissue type DCs, certain subpopulations of immature DCs in nonlymphoid tissues are positively regulated by TGF-beta1 signaling. In particular, epithelial-associated DC populations seem to critically require TGF-beta1 stimulation for development and function. Recent studies established that TGF-beta1 stimulation is absolutely required for the development of epithelial Langerhans cells (LCs) in vitro and in vivo. Furthermore, TGF-beta1 seems to enhance antigen processing and costimulatory functions of epithelial LCs.