Abstract
Tolerogenic dendritic cells (tolDCs) are central players in the initiation and maintenance of immune tolerance and subsequent prevention of autoimmunity. Recent advances in treatment of autoimmune diseases including systemic lupus erythematosus (SLE) have focused on inducing specific tolerance to avoid long-term use of immunosuppressive drugs. Therefore, DC-targeted therapies to either suppress DC immunogenicity or to promote DC tolerogenicity are of high interest. This review describes details of the typical characteristics of in vivo and ex vivo tolDC, which will help to select a protocol that can generate tolDC with high functional quality for clinical treatment of autoimmune disease in individual patients. In addition, we discuss the recent studies uncovering metabolic pathways and their interrelation intertwined with DC tolerogenicity. This review also highlights the clinical implications of tolDC-based therapy for SLE treatment, examines the current clinical therapeutics in patients with SLE, which can generate tolDC in vivo, and further discusses on possibility and limitation on each strategy. This synthesis provides new perspectives on development of novel therapeutic approaches for SLE and other autoimmune diseases.
Highlights
Dendritic cells (DCs) are antigen-presenting cells that act as immune sentinels, and play a central role in activation of immune responses and in mediation of immune homeostasis and immune tolerance [1,2]
Generation of Tolerogenic dendritic cells (tolDCs) using a single tolerogenic agent gave rise to tolDCs with different phenotypic and functional features [15,68]; these differences may result from variation in dosing and methods
There are limited data on specific strategies for tolDCs induction in systemic lupus erythematosus (SLE), the role of tolDCs in current therapies and clinical trials are under investigation
Summary
Dendritic cells (DCs) are antigen-presenting cells that act as immune sentinels, and play a central role in activation of immune responses and in mediation of immune homeostasis and immune tolerance [1,2]. Immunogenic DCs may be primarily induced by pathogens inflammatory signal molecules, and they typically promote effector function of adaptive immune cells [1,7]. Tolerogenic DCs (tolDCs) are induced by either anti-inflammatory signals or signals interfering with immunogenic DC function, and they play an important role in induction of immune tolerance, resolution of ongoing immune responses and prevention of autoimmunity by inhibiting effector and autoreactive T cells, and by triggering regulatory T cell (Treg) development [7,8,9]. The phenotypic and functional features of tolDCs required for effective therapy may differ based on the pathogenesis of distinct autoimmune diseases [14,17]. We discuss our current understanding of tolDCs and highlight some clinical implications for SLE treatment
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