BACKGROUNDAllogeneic transplantation immune tolerance is currently a hot research issue and soluble CD83(sCD83) is a novel immunomodulator with great potential in inducing transplantation tolerance.OBJECTIVETo investigate the mechanism of the immune tolerance effect of sCD83 on rat liver transplantation.METHODA rat liver transplantation model was established to study the effects of sCD83 on the expression levels of IL-2, IL-10, and TGF-β in peripheral blood and the mRNA expressions of foxp3, TGF-β, and Indoleamine 2,3-dioxygenase (IDO) in liver. The expression changes of costimulatory molecules CD80, CD86, and MHC-II on the surface of DC cells and the expressions of IDO ⁺ DC cell, TGF-β ⁺ CD4 ⁺ T cell, and CD4 ⁺ CD25 ⁺ Foxp3 ⁺ T cell were analyzed and compared.RESULTSsCD83 alleviated the rejection activity index (RAI) of rat liver transplantation in the early stage, increased the expressions of TGF-β, IL-10 in peripheral blood and the mRNAs of IDO, TGF-β and foxp3 in the transplanted liver, and down-regulated the expressions of MHC-II, CD86, and CD80 in DC cells, resulting in significant increased numbers of tolerogenic TGF-β ⁺ CD4 ⁺ T cells, Treg cells, and IDO ⁺ DC cells with low expression.CONCLUSIONsCD83 inhibited acute rejection after liver transplantation in an allogeneic rat, and the mechanism was associated with the effect that sCD83 increased the expression of TGF-β, activated IDO immunosuppressive pathway, and increased tolerogenic DC cells and Treg cells.

2014-11-01·Cellular Immunology3区 · 医学

Soluble CD83 inhibits human monocyte differentiation into dendritic cells in vitro

3区 · 医学

Article

作者: Wen, Jiexia ; Lin, Hongyu ; Li, Wenyan ; Liang, Shuang ; Zhong, Zhenyu ; Wang, Liyue ; Zhong, Fei ; Li, Xiujin ; Xu, Jian

Human CD83 is type I transmembrane glycoprotein, mainly expressed on mature dendritic cells (DCs), so it was first described as a molecular marker for mature DC. However, increasing evidence has demonstrated that CD83 is also an immunomodulatory molecule either its membrane-bound CD83 (mCD83) or soluble CD83 (sCD83) released from DCs. Intriguingly, the mCD83 possesses stimulatory effects on immune response, on the contrary, the sCD83 has inhibitory effects. Whether the sCD83 has the inhibitory effects on human monocyte differentiation into DCs is unknown. To this end, we prepared the recombinant human sCD83 in HEK293T cells and treated human monocytes being differentiated into DCs in vitro with the sCD83, and evaluate sCD83 inhibitory effects on immune response by analyzing the surface marker pattern of the cells. The results showed that the sCD83, especially glycosylated sCD83 could bind the monocytes and significantly inhibited the depression of CD14 expressions (P<0.01) and reduced CD1a, CD80, CD86 and MHC II expressions (P<0.01 or P<0.05) during the differentiation, indicating that the sCD83 can inhibit monocyte differentiation into DCs, and suggesting that a negative feedback regulation may exist in monocyte differentiation into DCs based on sCD83 released from the mature DCs.

Frontiers in Cell and Developmental Biology3区 · 生物学

Soluble CD83 Regulates Dendritic Cell–T Cell Immunological Synapse Formation by Disrupting Rab1a-Mediated F-Actin Rearrangement

3区 · 生物学

ArticleOA

作者: Su, Qinghong ; Zhou, Shuping ; Yu, Yong ; Lin, Wei ; Li, Xiaofan ; Feng, Meng

Dendritic cell–T cell (DC-T) contacts play an important role in T cell activation, clone generation, and development. Regulating the cytoskeletal protein rearrangement of DCs can modulate DC-T contact and affect T cell activation. However, inhibitory factors on cytoskeletal regulation in DCs remain poorly known. We showed that a soluble form of CD83 (sCD83) inhibited T cell activation by decreasing DC-T contact and synapse formation between DC and T cells. This negative effect of sCD83 on DCs was mediated by disruption of F-actin rearrangements, leading to alter expression and localization of major histocompatibility complex class II (MHC-II) and immunological synapse formation between DC and T cells. Furthermore, sCD83 was found to decrease GTP-binding activity of Rab1a, which further decreased colocalization and expression of LRRK2 and F-actin rearrangements in DCs, leading to the loss of MHC-II at DC-T synapses and reduced DC-T synapse formation. Further, sCD83-treated DCs alleviated symptoms of experimental autoimmune uveitis in mice and decreased the number of T cells in the eyes and lymph nodes of these animals. Our findings demonstrate a novel signaling pathway of sCD83 on regulating DC-T contact, which may be harnessed to develop new immunosuppressive therapeutics for autoimmune disease.

100 项与 sCD83(Mallia) 相关的药物交易

登录后查看更多信息