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

Abstract

Aim: Cumulative evidence has revealed that tolerogenic dendritic cells (tolDC) could relieve inflammation reactions in various autoimmune diseases. This study investigated the potential therapeutic application of vasoactive intestinal peptide (VIP)-induced tolDC (VIP-DC) on arthritis using collagen-induced arthritis (CIA) mice. Methods: Bone marrow cells were differentiated into dendritic cells (DC) using granulocyte macrophage colony-stimulating factor and interleukin (IL)-4. tolDC were induced by either VIP or Bay 11-7082 in vitro. Immunophenotypes and cytokine production of VIP-DC and Bay-DC were detected by fluorescence-activated cell sorting and enzyme-linked immunosorbent assay, respectively. Bay-DC, VIP-DC and untreated DC were ip administrated to CIA mice on day 40 when arthritis was onset. The treatment effects on arthritic and pathological changes, including synovial hyperplasia, pannus formation, inflammation and bone erosion, were assessed. Results: VIP-DC (40 ng/mL) and Bay-DC (0.5 µg/mL) had a lower level of major histocompatibility complex II, CD40 and CD86 expression, reduced γ-interferon and increased IL-4 production (P < 0.05 or 0.01), compared with untreated DC. The administration of VIP-DC and Bay-DC decreased the arthritis score clinically at the end of the therapy. Pathological assessments showed that bone erosion and inflammation were alleviated in the VIP-DC group compared with those in the untreated DC group (P < 0.05 and P < 0.01, respectively). Conclusion: VIP-DC showed reduced immunogenicity and enhanced anti-inflammatory cytokine production. Both VIP-DC and Bay-DC could ameliorate arthritis in CIA mice clinically. VIP-DC were not inferior to Bay 11-7082-induced tolDC but may exert a better preventive effect on bone destruction. K E Y W O R D S collagen-induced arthritis, rheumatoid arthritis, tolerogenic dendritic cell, vasoactive intestinal peptide

A short course of tofacitinib sustains the immunoregulatory effect of CTLA4-Ig in the presence of inflammatory cytokines and promotes long-term survival of murine cardiac allografts

“…Very interestingly, as also observed in human monocytes, 52 Tofa exposure does not prevent MHC‐II upregulation. The net result of such an altered phenotype would be the preservation of alloantigens presentation (Signal 1) with reduced Signals 2 and 3 (strengthening the effect of CTLA4‐Ig) and ultimately translating into a tolerogenic DC phenotype 56‐60 . We believe these regulatory effects contribute to the extension of transplant survival we observed.…”

A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases

“…In either case, the later administration in vivo of these cells produces Ag-specific Treg capable of inducing specific tolerance to naïve recipients. In this way, they cause the attenuation of symptoms of different animal models of autoimmune and/or inflammatory diseases, for example, in CIA arthritis, TNBS-induced colitis, EAE, sepsis, and spontaneous autoimmune peripheral polyneuropathy [177,[179][180][181][182]. In addition, in vitro studies with VIP have shown that it affects not only the phenotypic and functional maturation of DCs, but also the migration of these cells [183][184][185].…”

A short course of Tofacitinib sustains the immunoregulatory effect of CTLA4-Ig in presence of inflammatory cytokines and promotes long-term survival of murine cardiac allografts

“…The net result of such an altered phenotype would be the preservation of alloantigens presentation (Signal 1) with reduced Signal 2 and 3 (strengthening the effect of CTLA4-Ig) and ultimately translating into a tolerogenic DC phenotype. [55][56][57][58][59] We believe these regulatory effects contribute to the extension of transplant survival we observed, and we are further investigating this mechanistic aspect.…”