Abstract
Many neurologic diseases are related to autoimmune dysfunction and a variety of molecules or reaction pathways are involved in the regulation of immune function of the nervous system. Soluble CD83 (sCD83) is the soluble form of CD83, a specific marker of mature dendritic cell, which has recently been shown to have an immunomodulatory effect. Indoleamine 2,3-dioxygenase (IDO; corresponding enzyme intrahepatic, tryptophan 2,3-dioxygenase, TDO), a rate-limiting enzyme of extrahepatic tryptophan kynurenine pathway (KP) participates in the immunoregulation through a variety of mechanisms solely or with the synergy of sCD83, and the imbalances of metabolites of KP were associated with immune dysfunction. With the complement of sCD83 to IDO-KP, a previously known immunomodulatory axis, this review focused on an expanded neuroimmunomodulation axis: sCD83-IDO-KP and its involvement in nervous system diseases.
Highlights
SCD83 and ImmunomodulationCD83 is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily members [1], which is mainly expressed on membrane of mature dendritic cells (DCs) of human or mice [2], and considered as a specific marker of DCs
Guo et al isolated and purified Soluble CD83 (sCD83) molecules from Pichia pastoris [1]. sCD83 inhibited the differentiation process of monocytes into DCs in vitro and during which there was a feedback regulatory mechanism [6]. sCD83 inhibited the maturation of T cells and immature DCs stimulated by mature DCs [7] and the expression and release of CD83 from mature DC membranes induced by lipopolysaccharide
The enhanced IDO expression and increased KYN/ TRP ratio reflecting the activity of kynurenine pathway (KP) in tryptophan metabolism were observed in serum of Alzheimer’s Disease (AD) patients, exhibiting an inverse correlation with the cognitive decline [110]
Summary
CD83 is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily members [1], which is mainly expressed on membrane of mature dendritic cells (DCs) of human or mice [2], and considered as a specific marker of DCs. Staab et al established effective sCD83 expression and purification regimens with eukaryotic human embryonic kidney 293T cells [5]. SCD83 inhibited the differentiation process of monocytes into DCs in vitro and during which there was a feedback regulatory mechanism [6]. SCD83 inhibited the maturation of T cells and immature DCs stimulated by mature DCs [7] and the expression and release of CD83 from mature DC membranes induced by lipopolysaccharide. Mediated by IDO and transforming growth factor-β (TGF-β), the immunomodulatory effects of sCD83 were associated with CD4+CD25+Foxp3+ regulatory T cells (Tregs). Studies in vitro had shown that sCD83 induced long-term expression of IDO in DCs through autocrine or paracrine of TGF-β, whereas the latter was an essential cytokine for IDO-dependent immune tolerance [10]. SCD83 was involved in the pathogenesis of immune-related diseases, such as multiple sclerosis and its animal models of experimental autoimmune encephalomyelitis (EAE) [11], systemic lupus erythematosus (SLE) [8], transplant rejection [12, 13] and would probably provide promising approaches for the treatment of autoimmune diseases
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