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

Zhu,Feng; Qiu,Tingting; Zhu,Shengyun; Zhao,Kai; Chen,Chong; Qiao,Jianlin; Pan,Bin; Yan,Zhiling; Chen,Wei; Liu,Qiong; Wu,Qingyun; Cao,Jiang; Sang,Wei; Zeng,Lingyu; Sun,Haiying; Li,Zhenyu; Xu,Kailin

doi:10.3892/or.2020.7588

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

Authors:
- Feng Zhu
- Tingting Qiu
- Shengyun Zhu
- Kai Zhao
- Chong Chen
- Jianlin Qiao
- Bin Pan
- Zhiling Yan
- Wei Chen
- Qiong Liu
- Qingyun Wu
- Jiang Cao
- Wei Sang
- Lingyu Zeng
- Haiying Sun
- Zhenyu Li
- Kailin Xu
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Affiliations: Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China, Laboratory of Transplant Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
Published online on: April 21, 2020 https://doi.org/10.3892/or.2020.7588
Pages: 43-54
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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‑γ 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.

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