Catharina C Gross1, Heinz Wiendl. 1. Department of Inflammatory Disorders of the Nervous System and Neurooncology, Neurology Clinic, University Hospital Münster, Münster, Germany.
Abstract
PURPOSE OF REVIEW: Autoimmune diseases are the result of an imbalanced immune regulatory network. Tolerogenic dendritic cells (tolDCs) are key players of this network by inducing and maintaining both central and peripheral tolerance. Therefore, ex vivo generated tolDCs are considered as therapeutic vaccines to re-establish (antigen-specific) tolerance in autoimmune disorders. RECENT FINDINGS: TolDCs represent a heterogeneous group of dendritic cells that reside in different tissues and maintain tolerance by inducing anergy or apoptosis of autoreactive T cells, phenotypic skewing and induction of different types of regulatory T cells (Tregs). Both experimental animal models of autoimmune diseases and in vitro experiments with ex vivo generated human tolDCs have demonstrated their potency in re-establishing antigen-specific tolerance. The identified key mechanisms are induction of antigen-specific T cell anergy and/or promoting Tregs. SUMMARY: TolDCs represent an interesting strategy to re-establish antigen-specific tolerance and thus are considered as a treatment option for autoimmune diseases. First clinical trials are on the way. However, several technical and conceptual difficulties exist, ranging from the choice of antigen(s), dendritic cell generation protocols, to application regimens. This review discusses the state of this therapeutic concept including chances, perils and pitfalls.
PURPOSE OF REVIEW: Autoimmune diseases are the result of an imbalanced immune regulatory network. Tolerogenic dendritic cells (tolDCs) are key players of this network by inducing and maintaining both central and peripheral tolerance. Therefore, ex vivo generated tolDCs are considered as therapeutic vaccines to re-establish (antigen-specific) tolerance in autoimmune disorders. RECENT FINDINGS: TolDCs represent a heterogeneous group of dendritic cells that reside in different tissues and maintain tolerance by inducing anergy or apoptosis of autoreactive T cells, phenotypic skewing and induction of different types of regulatory T cells (Tregs). Both experimental animal models of autoimmune diseases and in vitro experiments with ex vivo generated human tolDCs have demonstrated their potency in re-establishing antigen-specific tolerance. The identified key mechanisms are induction of antigen-specific T cell anergy and/or promoting Tregs. SUMMARY: TolDCs represent an interesting strategy to re-establish antigen-specific tolerance and thus are considered as a treatment option for autoimmune diseases. First clinical trials are on the way. However, several technical and conceptual difficulties exist, ranging from the choice of antigen(s), dendritic cell generation protocols, to application regimens. This review discusses the state of this therapeutic concept including chances, perils and pitfalls.
Authors: Amandeep Bajwa; Liping Huang; Elvira Kurmaeva; Joseph C Gigliotti; Hong Ye; Jacqueline Miller; Diane L Rosin; Peter I Lobo; Mark D Okusa Journal: J Am Soc Nephrol Date: 2015-08-18 Impact factor: 10.121