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过继诱导抗原特异性 Treg 细胞逆转胶原诱导性关节炎小鼠模型的炎症。

Adoptive Induced Antigen-Specific Treg Cells Reverse Inflammation in Collagen-Induced Arthritis Mouse Model.

机构信息

Department of Orthopaedics, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.

Department of Rheumatology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.

出版信息

Inflammation. 2018 Mar;41(2):485-495. doi: 10.1007/s10753-017-0704-4.

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that may cause bone damage and worsening disability. Manipulating antigen-specific Treg cells is a promising approach to treat autoimmune disease since the immune suppressive function of Treg cells has the feature of antigen specificity which could avoid overall immune suppression. It has been known that the function of Treg cells is impaired in RA, and adoptive transfer of Treg cells is effective in suppressing RA. Here, we designed a new approach to generate antigen-specific Treg cells by culturing CD4 T cells from mice with RA onset, and we also proved that the adoptive transfer of these antigen-specific Treg cells reversed the collagen-induced arthritis (CIA) progression by suppressing the key inflammatory cytokine TNF-α. Further analysis showed that the transferred Treg cells were stable in vivo. These findings suggest this novel approach may have clinical applications for treatment of autoimmunity, including RA and other autoimmune disorders.

摘要

类风湿关节炎(RA)是一种系统性自身免疫性疾病,可能导致骨骼损伤和残疾加重。由于 Treg 细胞的免疫抑制功能具有抗原特异性的特点,因此可以避免全身免疫抑制,靶向抗原特异性 Treg 细胞是治疗自身免疫性疾病的一种很有前途的方法。已知 RA 患者的 Treg 细胞功能受损,过继转移 Treg 细胞可有效抑制 RA。在这里,我们设计了一种新方法,通过培养 RA 发病小鼠的 CD4 T 细胞来产生抗原特异性 Treg 细胞,我们还证明,通过抑制关键炎症细胞因子 TNF-α,过继转移这些抗原特异性 Treg 细胞可逆转胶原诱导性关节炎(CIA)的进展。进一步的分析表明,转移的 Treg 细胞在体内稳定。这些发现表明,这种新方法可能具有治疗自身免疫性疾病的临床应用,包括 RA 和其他自身免疫性疾病。

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