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TIRC7 inhibits Th1 cells by upregulating the expression of CTLA?4 and STAT3 in mice with acute graft?versus?host disease.

ABSTRACT: In a previous study, it was demonstrated that T?cell immune response cDNA 7 (TIRC7) levels reflect the efficacy of treatment of patients with acute graft?versus?host disease (GVHD). However, the pathogenesis of TIRC7 in acute GVHD remains poorly understood. Lymphocytes from patients with acute GVHD were selected as targeT cells, and the effects of TIRC7 on cytotoxic T lymphocyte antigen?4 (CTLA?4), T cell activation and cytokine secretion were observed by electroporation. A mouse model of acute GVHD was established; anti?TIRC7 and anti?CTLA?4 monoclonal antibodies were intraperitoneally injected into recipient mice. Then, the effects of TIRC7 and CTLA?4 on T cell activation and acute GVHD were monitored. After TIRC7 expression was downregulated, CTLA?4 levels were decreased and STAT3 phosphorylation was reduced; conversely, the activation capacity of T lymphocytes was elevated, and the secretion of interferon?? and other cytokines was increased. The mice in the TIRC7 + CTLA?4 co?administration group exhibited the lowest acute GVHD scores, with the longest average survival time and shortest recovery time of hematopoietic reconstitution. In conclusion, the results indicated that TIRC7 may positively regulate the function of CTLA?4 and inhibit T cell activation, thus suppressing the development and progression of acute GVHD.

SUBMITTER: Zhu F

PROVIDER: S-EPMC7254953 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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TIRC7 inhibits Th1 cells by upregulating the expression of CTLA‑4 and STAT3 in mice with acute graft‑versus‑host disease.

Zhu Feng F Qiu Tingting T Zhu Shengyun S Zhao Kai K Chen Chong C Qiao Jianlin J Pan Bin B Yan Zhiling Z Chen Wei W Liu Qiong Q Wu Qingyun Q Cao Jiang J Sang Wei W Zeng Lingyu L Sun Haiying H Li Zhenyu Z Xu Kailin K

Oncology reports 20200421 1

In a previous study, it was demonstrated that T‑cell immune response cDNA 7 (TIRC7) levels reflect the efficacy of treatment of patients with acute graft‑versus‑host disease (GVHD). However, the pathogenesis of TIRC7 in acute GVHD remains poorly understood. Lymphocytes from patients with acute GVHD were selected as targeT cells, and the effects of TIRC7 on cytotoxic T lymphocyte antigen‑4 (CTLA‑4), T cell activation and cytokine secretion were observed by electroporation. A mouse model of acute ...[more]

PMID: 32319655

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Project description:BackgroundIn this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model.Methodology/principal findingsMixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4(+) splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4(+)Foxp3(+) splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4(+) regulatory T cells (Tregs) as well as CD8(+) Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations.Conclusion/significanceIn the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4(+) and CD8(+) Treg) cell lineages as well as B cell homeostasis.

Dataset Information

TIRC7 inhibits Th1 cells by upregulating the expression of CTLA?4 and STAT3 in mice with acute graft?versus?host disease.

Publications

TIRC7 inhibits Th1 cells by upregulating the expression of CTLA‑4 and STAT3 in mice with acute graft‑versus‑host disease.

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