Tolerogenic Dendritic Cells Induced by BD750 Ameliorate Proinflammatory T cell Responses and Experimental Autoimmune Encephalitis in Mice

Zhou, Yan; Leng, Xiao; Li, Hua; Yang, Shuxia; Tai, Yang; Li, Limei; Xiong, Ying; Zou, Qiang; Liu, Yang; Wang, Yantang

doi:10.2119/molmed.2016.00110

Cited by 14 publications

(17 citation statements)

References 29 publications

(36 reference statements)

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“…Natural products, such as Apigenin and Estriol, have also been found to induce DCregs, which play a therapeutic function in EAE mice (Papenfuss et al, 2011;Ginwala et al, 2016). Our previous findings suggested that tolerogenic DCs modified by the benzothiazole derivative BD750 can ameliorate EAE in mice, and a similar result was found by our group for tofacitinibinduced tolerogenic DCs (Zhou et al, 2016;Zhou et al, 2017). Though DCregs therapy is a potential method for the treatment of EAE and MS, several problems still require solving.…”

Section: Introductionsupporting

confidence: 72%

“…Antigen peptide-loaded DCregs are effective in treating models of autoimmune disorders due to their tolerogenic characteristics and ability to suppress the responses of antigen-specific T cells (Zhou et al, 2016;Zhou et al, 2017). For clinical treatment, the agents used for DCreg induction should be safe, efficient, and have low toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Female C57BL/6 mice (6-8 weeks) were immunized subcutaneously with 200 mg of MOG 35-55 peptide, as previously described (Zhou et al, 2017). Each mouse was injected with 500 ng pertussis toxin (PTx) i.p.…”

Section: Experimental Autoimmune Encephalitis Induction and Adoptive mentioning

confidence: 99%

“…DCregs induced by 1, 25-Dihydroxyvitamin D 3 (1,25-D3) (10 -8 M; Sigma-Aldrich) were used as a positive control. The development of EAE was observed daily, and clinical scores were made according to the Benson score: 0, no clinical signs; 1, paralyzed tail; 2, loss of coordinated movement, hind limb paresis; 3, both hind limbs paralyzed; 4, forelimbs paralyzed; and 5, moribund (Zhou et al, 2017).…”

Section: Experimental Autoimmune Encephalitis Induction and Adoptive mentioning

confidence: 99%

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Regulatory Dendritic Cells Induced by K313 Display Anti-Inflammatory Properties and Ameliorate Experimental Autoimmune Encephalitis in Mice

et al. 2020

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As a GSK-3b inhibitor reported by our group, K313 is a novel benzoxazole derivative and displays anti-inflammatory properties in RAW264.7 macrophages without cytotoxicity. The activity of GSK-3b affects the differentiation and maturation of bone marrow-derived dendritic cells (DCs). This study aims to investigate whether K313 can be used to induce regulatory/tolerogenic dendritic cells (DCregs), and the therapeutic effects of DCregs induced by K313 in the autoimmune model of experimental autoimmune encephalitis (EAE). The results show that compared with LPS stimulated mature DCs, K313-treated bone marrow-derived DCs display obvious tolerogenic characteristics with decreased expression of co-stimulatory molecules, downregulated secretions of pro-inflammatory cytokines and unregulated secretion of anti-inflammatory cytokine IL-10. The above characteristics conform to the typical phenotypes of DCregs. Moreover, K313-modified DCregs inhibit antigen-specific T cell responses in vitro. Furthermore, by adoptive transfer, K313 modified DCregs to the EAE mice, and the development of disease was ameliorated to some extent. In addition, treatment with K313-modified DCregs also significantly reduced the percentages of splenetic Th1 and Th17 cells and increased the percentage of regulatory T cells in EAE mice. In conclusion, K313-modified DCregs show anti-inflammatory properties in vitro and have a significant positive effect on the EAE disease in vivo. Our data indicate that K313-induced DCregs pulsed with auto-antigen might have potential use as a therapeutic approach for autoimmune inflammation of the central nervous system.

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Section: Introductionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Autoimmune Encephalitis Induction and Adoptive mentioning

confidence: 99%

Section: Experimental Autoimmune Encephalitis Induction and Adoptive mentioning

confidence: 99%

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Regulatory Dendritic Cells Induced by K313 Display Anti-Inflammatory Properties and Ameliorate Experimental Autoimmune Encephalitis in Mice

et al. 2020

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“…Previous work has implicated the tolerogenic plasmacytoid DCs in lymph nodes in generating donor-specific peripheral FoxP3+ Treg cells in an allo-cardiac transplantation mouse model treated with anti-CD154 mAb and donor-specific transfusion (DST) 58 . Moreover, immunogenic DCs, which are triggered by CD40 signaling, have been shown to convert into tolerogenic DCs when JAK3, a downstream molecule of CD40, is inhibited 59 , 60 . We assume that the production of costimulatory molecules and inflammatory cytokines for immunogenic DC activation may be hampered by inhibited CD40 signaling 61 , 62 , thus driving them into tolerogenic DCs.…”

Section: Discussionmentioning

confidence: 99%

Donor-Specific Regulatory T Cell-Mediated Immune Tolerance in an Intrahepatic Murine Allogeneic Islet Transplantation Model with Short-Term Anti-CD154 mAb Single Treatment

et al. 2020

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Anti-CD154 blockade-based regimens remain unequaled in prolonging graft survival in various organ transplantation models. Several studies have focused on transplantation tolerance with the anti-CD154 blockade, but none of these studies has investigated the mechanisms associated with its use as the sole treatment in animal models, delaying our understanding of anti-CD154 blockade-mediated immune tolerance. The purpose of this study was to investigate the mechanism underlying the anti-CD154 monoclonal antibody (mAb) blockade in inducing immune tolerance using an intrahepatic murine allogeneic islet transplantation model. Allogeneic BALB/c AnHsd (BALB/c) islets were infused into the liver of diabetic C57BL/6 (B6) mice via the cecal vein. Anti-CD154 mAb (MR1) was administered on −1, 0, 1, 3, 5, and 7 d posttransplantation at 0.5 mg per mouse. We showed that short-term MR1 monotherapy could prolong the allogeneic islet grafts to more than 250 d in the murine intrahepatic islet transplantation model. The second islet grafts transplanted under the kidney capsule of the recipients were protected from rejection. We also found that rejection of same-donor skin grafts transplanted to the tolerant mice was modestly delayed. Using a DEREG mouse model, FoxP3+ regulatory T (Treg) cells were shown to play important roles in transplantation tolerance. In mixed lymphocyte reactions, Treg cells from the tolerant mice showed more potency in suppressing BALB/c splenocyte-stimulated Teff cell proliferation than those from naïve mice. In this study, we demonstrated for the first time that a short-term anti-CD154 mAb single treatment could induce FoxP3+ Treg cell-mediated immune tolerance in the intrahepatic murine allogeneic islet transplantation model.

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Alleviation of experimental autoimmune encephalomyelitis by transferring low RelB expression tolerogenic dendritic cells

Zheng,

Liu,

Liu

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Tolerogenic Dendritic Cells Induced by BD750 Ameliorate Proinflammatory T cell Responses and Experimental Autoimmune Encephalitis in Mice

Cited by 14 publications

References 29 publications

Regulatory Dendritic Cells Induced by K313 Display Anti-Inflammatory Properties and Ameliorate Experimental Autoimmune Encephalitis in Mice

Regulatory Dendritic Cells Induced by K313 Display Anti-Inflammatory Properties and Ameliorate Experimental Autoimmune Encephalitis in Mice

Donor-Specific Regulatory T Cell-Mediated Immune Tolerance in an Intrahepatic Murine Allogeneic Islet Transplantation Model with Short-Term Anti-CD154 mAb Single Treatment

Alleviation of experimental autoimmune encephalomyelitis by transferring low RelB expression tolerogenic dendritic cells

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