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Objective To evaluate the role of recombinant human soluble Tim-3 (hTim-3-Fc) in regulating immune response.Methods Soluble hTim-3 was incubated with human macrophage cell line U 937, human T cell line Jurkat and normal human PBMC before cytokines secreted by or expressed in different immune cells were analyzed using ELISA , RT-PCR and Western-blotting, respectively.Results Soluble hTim-3 significantly promoted the activation of different immune cells.Our data showed that IL-8 secretion by U937 cells, IL-2 secretion by Jurkat cells , IL-2 and IFN-γsecretion by human PBMCs were all significantly increased .In addition , soluble hTim-3 significantly increased the IFN-α2 and IFN-β1 mRNA expression in U937, Jurkat and PBMCs and increased the phosphorylation of stat-1 in Jurkat and U937 cells.Conclusion Recombinant soluble hTim-3 can significantly promote the activation of immune cells in vitro, which shows its therapeutic potential .
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The lung is a major damage tissue in paraquat(PQ)-caused acute poisoned patients. Most deaths from acute PQ poisoning can be attributed to acute lung injury(ALI). Complement activa?tion product C5a causes inflammatory cells,such as neutrophils and macrophages,to accumulate into the lung and get activated. These activated inflammatory factors generate a large number of oxidants and inflammatory sequelae named cytokine storm to mediate ALI induced by PQ poison. The review focused on the role and mechanisms of complement C5a in PQ-induced ALI.
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Objective To ascertain whether estrogen could induce B cell to produce interleukin(IL)-10. Methods C57BL/6 splenic B cells were purified by magnetic activated cell sorting(MACS)method,followed by estrogen treatment for 3 days. The secretion of IL-10 from cultured cell supernatant was tested by ELISA technique. The abundance of mRNA for IL-10、PD-L1 and RBM47 in B cells with estrogen treatment was tested by real-time PCR method. The intracellular IL-10 expression and the surface PD-L1 expression of treated B cells were tested by fluorescence activated cell sorting(FACS)method. And the expression of RBM47 in B cells by estrogen treatment was tested using Western blotting method. Results Estrogen could induce B cell to produce IL-10 in a dose-dependent manner. Estrogen treatment could increase the percentage of IL-10+B cells,the abundance of mRNA for IL-10,PD-L1 and RBM47 in B cells,as well as the expression of PD-L1 on B cell surface. Furthermore,our experimental result indicated the upreg?ulation of RBM47 expression in B cells by estrogen treatment. Conclusion Estrogen treatment in vitro can induce the upregulation of IL-10+regulatory B cells(Breg). Upregulation of RBM47 in the treated B cells might participate in this process by stabilizing IL-10 mRNA.
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Objective To examine whether Tim-3 plays a protective role in paraquat poisoning induced excessive immune response and tissue damage based on the critical roles of Tim-3 controlling inflammatory response.Methods A paraquat poisoning model was established in wild type and in Tim-3 transgenic C57BL/6 mice by intraperitoneal injection of paraquat (40 mg/kg) .In addition, C57BL/6 mice with paraquat poisoning were injected with Tim-3 soluble protein( sTim-3) or control protein to see the effect of Tim-3 blocking on the progression of paraquat poisoning.Samples were collected at 6 and 24 h after paraquat injection respectively and were examined for tissue damage, cytokine expression and paraquat metabolism.Results After paraquat poisoning, there was significantly attenuated tissue damage in the lungs and kidneys and decreased TNF-α,IL-6 and IL-1 beta expression in the PBMCs or in the serum from Tim-3 transgenic mice compared to wild type mice.The serum concentration of paraquat in Tim-3 transgenic mice was also significantly decreased.However, in sTim-3 treated paraquat poisoning mice, there was significantly increased cytokine expression and tissue damage compared to control protein treated mice.The in vitro data showed that Tim-3 signaling negatively regulated macrophages mediated inflammatory response.Conclusion Tim-3 plays a critical role in maintaining the homeostasis after paraquat poisoning. Further investigation on the regulatory roles of Tim-3 in inflammation will shed new light on the pathogenesis of paraquat poisoning and provide new therapeutic strategies.
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B cells not only can regulate the immune responses by producing antibody, presenting antigens to target immune cells, but also have the function of immune suppression. A small quantity of regulatory B ( Breg) cells in vivo is capable of performing regulatory functions by producing of inhibitory cytokines,such as interleukin -10, or by direct interaction with other immune cells. In vivo, Breg can maintain immune tolerance and inhibit excessive inflammatory responses efficiently. Clinical studies indicate that Breg are associated with some autoimmune diseases, cancers, infections, and transplantation tolerance. The review focuses on molecules associated with the differentiation and function of the Breg. And also, we discuss the mechanisms and the relations of Breg to clinical diseases.
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Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease model mediated by specific allergenic CD4+T cell and accompanied by mononuclear cells invasion in central nervous system (CNS) and demyelination. Similar to the histopathology and immune characters of multiple sclerosis(MS), EAE has been used as a classical animal model for the study of MS. In recent years, as an immune regulator for the treatment of relapsing-remitting MS, study of estrogen has entered the pre-clinical phaseⅡtrials. Larger numbers of studies have verified that high concentration of estrogen could improve EAE. However, the specific mechanisms are still in controversy. For these considerations, this review summarizes the protective mechanisms of estrogen in EAE.
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The interleukin-12 (IL-12) family, including IL-12, IL-23, IL-27,and IL-35, is characterized by unique structures and molecular partners.This is the only family of heterodimeric cytokines, which endows them with a unique set of connections and functional interactions.They not only play an important role in the regulation of inflammation, but are closely related to various autoimmune diseases.Here we discuss the structural aspects of these cytokines and their effect on some autoimmune diseases.
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Multiple sclerosis(MS)is a demyelinating disease of the central nervous system and one of the most common autoimmune diseases,characterized by wide-spread lesions and relapsing-remitting encephalomyelitis,accompanied by optic nerve damage.Patients worldwide total about 2.5 million,mostly young adults and women.This disease remains incurable. Dimethylfumarate (DMF)is a new oral drug for MS,which was approved by the FDA in 2013 for clinical treatment of re-lapsing-remitting MS.It can reduce the activity of disease,and the relapsing-remitting MS relapse.This paper outlines the application of DMF to the treatment of MS and its mechanism of action.
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Objective To develop a human Tim-3 specific monoclonal antibody and evaluate its biological activity and possible use in clinical diseases associated with dysregulated Tim-3 expression .Methods The BALB/c mice were immu-nized by conventional method, and positive clones were used to develop anti-human Tim-3 antibody, the binding and neutralization activities of which in vitro and in vivo were investigated.Results ①A monoclonal antibody (clone L3D) which could specifically bind to human Tim-3 protein in ELISA assay was obtained and the subtype of the monoclonal antibody was IgG2a .②Flow cytometry indicated that the monoclonal antibody could bind to Tim-3 expressed in human U937 cells.This antibody also showed a cross activity to mice′Tim-3.③The monoclonal antibody inhibited the apoptosis of THP1 cells induced by Gal-9, the ligand of Tim-3.④Injection of Tim-3 antibody exacerbated sepsis in mice as marked by the decreased survival rate and increased expression of pro-inflammatory cytokines .Conclusion An anti-human Tim-3 monoclonal antibody is successfully obtained.The excellent binding and neutralization activities of this antibody enable it to be widely used in clinical diseases associated with deregulated Tim-3 expression .