Dendritic cells a double-edge sword in autoimmune responses

Abstract

Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in regulating innate and adaptive immune responses. In autoimmunity, DC act as a double-edged sword since on one hand they initiate adaptive self-reactive responses and on the other they play a pivotal role in promoting and maintaining tolerance. Thus, DC are the most important cells in either triggering self-specific responses or in negatively regulating auto-reactive responses. The latter function is mediated by DC in the steady-state or specialized subsets of DC, named tolerogenic DC. Clinical and experimental evidence indicate that prolonged presentation of self-antigens by DC is crucial for the development of destructive autoimmune diseases, and defects in tolerogenic DC functions contribute to eradication of self-tolerance. In recent years, DC have emerged as therapeutic targets for limiting their immunogenicity against self-antigens, while tolerogenic DC have been conceived as therapeutic tools to restore tolerance. The purpose of this review is to give a general overview of the current knowledge on the pathogenic role of DC in patients affected by autoimmune diseases. In addition, the protective role of tolerogenic DC will be addressed. The currently applied strategies to block immune activation or to exploit the tolerogenic potential of DC will be discussed.

Endosome-mediated autophagy

“…Second, constitutive autophagy in DCs could be important for their function in conferring central and peripheral immune tolerance. 70 Finally, they could play an important role in coordinating the process of antigen presentation by both MHC class I and MHC class II molecules and T cell activation. In this regard, a recent in vivo study in mice with DC-specific Atg5 deletion suggested that autophagy is required for MHC class II-mediated antigen presentation.…”

Regulatory dendritic cells in autoimmunity: A comprehensive review

“…The breakdown of the balance between DC-mediated immune activation and tolerance plays central role in the initiation and progression of autoimmune diseases. Next we will discuss current understanding on the dysregulated DC activation in the development of autoimmune diseases, taking inflammatory bowel disease (IBD) as an example [137,138].…”

An Increase in Tolerogenic Dendritic Cell and Natural Regulatory T Cell Numbers during Experimental Autoimmune Encephalomyelitis in Rras−/− Mice Results in Attenuated Disease

“…Although DC are essential for conferring protection against pathogens, they can also initiate self-reactive immune responses leading to autoimmunity. In contrast, DC play important roles in controlling autoimmune responses by maintaining tolerance (12-14). DC endowed with negative immune-regulatory functions are termed tolerogenic DC and have been reported to express lower surface expression of co-stimulatory and major histocompatibility complex class II (MHCII) molecules (15-18).…”