TIRC7 inhibits Th1 cells by upregulating the expression of CTLA‑4 and STAT3 in mice with acute graft‑versus‑host disease.
Animals
Antibodies, Monoclonal
/ pharmacology
CTLA-4 Antigen
/ antagonists & inhibitors
Disease Models, Animal
Gene Expression Regulation
Graft vs Host Disease
/ genetics
Humans
Lymphocyte Activation
/ drug effects
Male
Mice
STAT3 Transcription Factor
/ genetics
Th1 Cells
/ drug effects
Vacuolar Proton-Translocating ATPases
/ antagonists & inhibitors
T-cell immune response cDNA 7
T helper 1 cells
cytotoxic T lymphocyte antigen‑4
STAT3
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
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
43-54Références
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