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


Journal

Oncology reports
ISSN: 1791-2431
Titre abrégé: Oncol Rep
Pays: Greece
ID NLM: 9422756

Informations de publication

Date de publication:
07 2020
Historique:
received: 13 12 2018
accepted: 18 03 2020
pubmed: 23 4 2020
medline: 9 3 2021
entrez: 23 4 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32319655
doi: 10.3892/or.2020.7588
pmc: PMC7254953
doi:

Substances chimiques

Antibodies, Monoclonal 0
CTLA-4 Antigen 0
CTLA4 protein, human 0
STAT3 Transcription Factor 0
STAT3 protein, human 0
TCIRG1 protein, human 0
Vacuolar Proton-Translocating ATPases EC 3.6.1.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

43-54

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Auteurs

Feng Zhu (F)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Tingting Qiu (T)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Shengyun Zhu (S)

Laboratory of Transplant Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Kai Zhao (K)

Laboratory of Transplant Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Chong Chen (C)

Laboratory of Transplant Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Jianlin Qiao (J)

Laboratory of Transplant Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Bin Pan (B)

Laboratory of Transplant Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Zhiling Yan (Z)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Wei Chen (W)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Qiong Liu (Q)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Qingyun Wu (Q)

Laboratory of Transplant Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Jiang Cao (J)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Wei Sang (W)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Lingyu Zeng (L)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Haiying Sun (H)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Zhenyu Li (Z)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

Kailin Xu (K)

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.

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Classifications MeSH