Tolerogenic dendritic cells and rheumatoid arthritis: current status and perspectives

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the influxation of synovia and synovial compartments with immune cells including dendritic cells (DCs). DCs that induce autoimmune tolerance are called tolerogenic DCs (tolDCs). As a promising immunotherapeutic strategy for RA, tolDCs have received increasing attention. In this review, we first introduce the significant role of tolDCs in autoimmune regulation and then describe the manipulation strategies to generate tolDCs; next, we summarize recent progress in the experimental application of tolDCs for RA therapy, and finally we discuss the perspectives of tolerogenic vaccination for the treatment for RA in clinic.

A Mouse Model of Adoptive Immunotherapeutic Targeting of Autoimmune Arthritis Using Allo-Tolerogenic Dendritic Cells

“…The inflammatory process in RA involves symmetrical and often bilateral swelling of the joints that reflects hyperplasia of the synovial membrane and a cellular infiltration by monocytes, macrophages, T and B cells, mast cells and dentritic cells (DCs) [1]. Current approaches for treating RA use immunosuppressive drugs and biological agents, which might induce generalized immune suppression and an increased risk of opportunistic infections [2]. Thus, new therapeutic approaches should be aimed at dampening inflammation and promoting tolerance toward arthritic antigens without compromising protective host immunity [3].…”

Vasoactive intestinal peptide‐induced tolerogenic dendritic cells attenuated arthritis in experimental collagen‐induced arthritic mice

“…DC, which constitute the front‐line defense against pathogens, are professional antigen‐presenting cells (APC) that are specialized in capturing and processing Ag to present to T cells. One specialized subset of DC, known as tolDC, promote and maintain tolerance through the presentation of Ag with inadequate co‐stimulation and cytokine production for effector T‐cell activation, resulting in T‐cell silencing or deletion or induction of Treg . RA is partially characterized by the excessive activation and infiltration of T cells toward the synovium and synovial compartments.…”

Antigen-Specific Tolerogenic Dendritic Cells Ameliorate the Severity of Murine Collagen-Induced Arthritis

“…RA is a common chronic autoimmune disease characterized by the infiltration of inflammatory cells and immune cells into the synovial and joint compartments. DCs have been identified as one of the major types of immune cells associated with RA, and a subgroup of DCs, referred to as tolDCs, can induce autoimmune tolerance [ 5 ]. tolDCs have received increasing attention as a promising immunotherapeutic strategy for RA.…”

“…Therefore, new therapeutic approaches are needed to control disease progression without compromising the immune system of the patient [ 4 ]. Many types of immune cells are involved in the pathogenesis and progression of RA, including dendritic cells (DCs), monocytes and macrophages, T and B lymphocytes, neutrophils and natural killer (NK) cells [ 5 ]. DCs are professional antigen-presenting cells (APCs) that have the capacity to stimulate or to inhibit immune responses [ 6 ].…”