Antithymocyte globulin combined with cyclosporine A down-regulates T helper 1 cells by modulating T cell immune response cDNA 7 in aplastic anemia

Zhu, Feng; Qiao, Jianlin; Wu, Qingyun; Chen, Wei; Yao, Yao; Niu, Mingshan; Fu, Chunling; Zeng, Lingyu; Li, Zhenyu; Xu, Kailin

doi:10.1007/s12032-015-0647-2

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…Meanwhile, our previous study also found that CTLA-4 levels were decreased in patients with aGVHD before aGVHD treatment (corticosteroids as the first-line standard treatment for II-IV aGVHD) (18), whereas they were increased in patients with aGVHD after treatment (6). However, TIRC7, a novel membrane molecule, has been shown to be an essential molecule in the regulation of lymphocyte activation, and its expression is increased prior to aGVHD treatment (corticosteroids as the first-line standard treatment for II-IV aGVHD) but decreased following treatment (6,18,30). A previous study demonstrated that TIRC7 plays an important regulatory function in both T and B cell responses (19).…”

Section: Discussionmentioning

confidence: 99%

Role of T cell immune response cDNA 7 on the pathology of acute graft‑versus‑host disease

Zhu

Fan

et al. 2020

Oncol Lett

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Activation of T lymphocytes is the initiating factor of the occurrence of acute graft-versus-host disease (aGVHD), and cytotoxic T lymphocyte antigen-4 (CTLA-4) is the inhibitory receptor for activating T cells. T cell immune response cDNA 7 (TIRC7) is considered an upstream regulator of CTLA-4; however, little is understood regarding the effects of TIRC7 on the regulation of CTLA-4 in aGVHD. The purpose of the present study was to evaluate the regulatory effects of TIRC7 on aGVHD, mainly in the pathology. Recipient mice were exposed to a preconditioning dose of 7.5 Gy irradiation on the day of the transplantation and were divided into the following groups: Blank control group, bone marrow transplantation control group, total body irradiation group, mild-moderate aGVHD group and severe aGVHD group. According to the different administration of CTLA-4 and TIRC7 monoclonal antibodies, the mild-moderate and severe aGVHD groups were randomly divided into the hematopoietic stem cell transplantation (HSCT) and HSCT + CTLA-4/TIRC7 groups. Recipient mice were sacrificed at different time points post-HSCT for histopathological analysis by hematoxylin and eosin staining. Compared with the control and other experimental groups, the mice in the combined CTLA-4 and TIRC7 group exhibited ameliorated pathological injury, and lower pathology scores of the liver, lung and intestine. These data revealed that intraperitoneal injection of anti-TIRC7 and/or anti-CTLA-4 monoclonal antibody into mice could effectively alleviate the severity of aGVHD.

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Section: Discussionmentioning

confidence: 99%

Role of T cell immune response cDNA 7 on the pathology of acute graft‑versus‑host disease

Zhu

Fan

et al. 2020

Oncol Lett

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“…Analysis of Th cells via f low cytometr y was performed as previously described (14). Anti-CD3-FITC (cat.…”

Section: Construction Of Pgpu6-shtirc7 and Flag-ctla-4mentioning

confidence: 99%

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

et al. 2020

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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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“… 12 Overall, studies have characterized the clinical relevance of type 1 immune reactions in patients with acquired AA, and the corresponding therapeutic strategy has begun to take advantage of the down-regulation in Th1 cells to reverse the loss of HSCs. 13 , 14 …”

Section: Introductionmentioning

confidence: 99%

IL-11 promotes the treatment efficacy of hematopoietic stem cell transplant therapy in aplastic anemia model mice through a NF-κB/microRNA-204/thrombopoietin regulatory axis

et al. 2017

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Hematopoietic stem cell (HSC) transplantation could be of therapeutic value for aplastic anemia (AA) patients, and immunosuppressants may facilitate the efficiency of the procedure. As anti-inflammatory cytokine interleukin-11 (IL-11) has a thrombopoietic effect, its use in cases of chronic bone marrow failure, such as AA, has been proposed to induce HSC function. However, the putative mechanisms that may support this process remain poorly defined. We found that decreased miR-204-5p levels were coincident with increased proliferation in mouse HSCs following exposure to IL-11 in vitro. Through inhibiting NF-кB activity, miR-204-5p repression was demonstrated to be a downstream effect of IL-11 signaling. miR-204-5p was shown to directly target thrombopoietin (TPO) via sequence-dependent 3′-UTR repression, indicating that this microRNA-dependent pathway could serve an essential role in supporting IL-11 functions in HSCs. Increased TPO expression in HSCs following IL-11 exposure could be mimicked or blocked by inhibiting or overexpressing miR-204-5p, respectively. Consistent with these in vitro findings, IL-11 promoted HSC engraftment in a mouse model of AA, an effect that was attenuated in cells overexpressing miR-204-5p. The reduction in miR-204-5p levels is an integral component of IL-11 signaling that may play an essential role in treating AA.

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Antithymocyte globulin combined with cyclosporine A down-regulates T helper 1 cells by modulating T cell immune response cDNA 7 in aplastic anemia

Cited by 5 publications

References 29 publications

Role of T cell immune response cDNA 7 on the pathology of acute graft‑versus‑host disease

Role of T cell immune response cDNA 7 on the pathology of acute graft‑versus‑host disease

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

IL-11 promotes the treatment efficacy of hematopoietic stem cell transplant therapy in aplastic anemia model mice through a NF-κB/microRNA-204/thrombopoietin regulatory axis

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