Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Dong, Peiyuan; Chen, Lingyun; Wu, Huimeng; Huo, Jiali; Jiang, Zhongxing; Shao, Yijun; Ren, Xiang; Huang, Jinbo; Li, Xingxin; Wang, Min; Nie, Neng; Zhang, Jing; Jin, Peng; Zheng, Yizhou; Ge, Meili

doi:10.3324/haematol.2021.280292

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…Feng et al have recently reported that PMN-MDSCs potently suppress T cell-mediated BM failure using a mouse model of immune-mediated aplastic anemia [82]. Conceptionally, these data are similar to those of Dong et al who reported that patients with severe immune-mediated aplastic anemia have fewer circulating M-MDSCs that possess impaired immunosuppressive activity [83].…”

Section: Potential Mechanism Involved In Suppressing Disease In Outbr...supporting

confidence: 74%

Influence of Housing Temperature and Genetic Diversity on Allogeneic T Cell-Induced Tissue Damage in Mice

Enriquez,

McDaniel Mims,

Stroever

et al. 2023

Pathophysiology

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The objective of this study was to determine how housing temperature and genetic diversity affect the onset and severity of allogeneic T cell-induced tissue damage in mice subjected to reduced intensity conditioning (RIC). We found that adoptive transfer of allogeneic CD4+ T cells from inbred donors into sub-lethally irradiated inbred recipients (I→I) housed at standard housing temperatures (ST; 22–24 °C) induced extensive BM and spleen damage in the absence of injury to any other tissue. Although engraftment of T cells in RIC-treated mice housed at their thermo-neutral temperature (TNT; 30–32 °C) also developed similar BM and spleen damage, their survival was markedly and significantly increased when compared to their ST counterparts. In contrast, the adoptive transfer of allogeneic T cells into RIC-treated outbred CD1 recipients failed to induce disease in any tissue at ST or TNT. The lack of tissue damage was not due to defects in donor T cell trafficking to BM or spleen but was associated with the presence of large numbers of B cells and myeloid cells within these tissues that are known to contain immunosuppressive regulatory B cells and myeloid-derived suppressor cells. These data demonstrate, for the first time, that housing temperature affects the survival of RIC-treated I→I mice and that RIC-conditioned outbred mice are resistant to allogeneic T cell-induced BM and spleen damage.

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Section: Potential Mechanism Involved In Suppressing Disease In Outbr...supporting

confidence: 74%

Influence of Housing Temperature and Genetic Diversity on Allogeneic T Cell-Induced Tissue Damage in Mice

Enriquez,

McDaniel Mims,

Stroever

et al. 2023

Pathophysiology

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“…S2). Previous research has pointed to a signi cant decrease in MDSC proportions in AA, linked to a noticeable reduction in immunosuppressive capabilities [20]. Employing ow cytometry-based sorting, we isolated MDSCs from both HDs and AA patients for Smart-seq analysis.…”

Section: Nk Cells With a Less Functional Cd56 Dim Molecular Signature...mentioning

confidence: 99%

“…CAA primarily results from genetic mutations, with the diagnosis of congenital bone marrow failure relying mainly on NGS sequencing. In AA, MDSCs exert immunosuppressive effects, leading to a signi cant decrease in their components [20]. We further evaluated the percentage of HLA-DR − CD11b + CD33 + MDSCs in AA and CAA, revealing a marginal decrease in MDSCs in AA compared to the HDs.…”

Section: Nk Cells With a Less Functional Cd56 Dim Molecular Signature...mentioning

confidence: 99%

Comprehensive mapping of immune perturbations associated with aplastic anemia

Wang,

Chen,

Deng

et al. 2024

Preprint

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Background Acquired aplastic anemia (AA) is an immune-mediated syndrome resulting in bone marrow failure. Therefore, comprehending the profile and cell interactions in affected patients is crucial. Methods Human peripheral blood mononuclear cells (PBMCs) were collected from both healthy donors (HD) and AA patients, and analyzed using multicolor flow cytometry. Utilizing FlowSOM, we explored and visualized the immunophenotypic and metabolic characteristics of AA. Results Patients with AA show increased CD56+ monocytes with NK characteristics and activated cytotoxic T cells in peripheral blood compared to HD. Conversely, less functional CD56dim NK cells, regulatory T cells and myeloid-derived suppressor cells (MDSCs) decrease in AA. Additionally, MDSCs demonstrate post-treatment recovery and can serve as clinical indicators to distinguish between acquired aplastic anemia (AA) and congenital aplastic anemia (CAA). We assessed correlations among 29 immune cell types and found that a significant increase in memory B cells, eosinophils, and NK bright cells, along with a marked decrease in NK dim and non-classic monocytes, indicates a discernible interplay and correlation among these immune cell populations. Conclusion Our study results demonstrate significant immune dysregulation in patients with AA. Thus, CD56+ monocytes with NK characteristics, activated cytotoxic T cells, less functional CD56dim NK cells, Treg cells, and MDSCs may play crucial roles in the onset and progression of AA, serving as potential diagnostic biomarkers. These findings are expected to facilitate accurate diagnosis and timely treatment, thereby reducing the high mortality rate.

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N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability

Liu

Li²,

Zhang³

et al. 2022

J Cancer Res Clin Oncol

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N 6 -methyladenosine (m 6 A) modi cation is pivotal transcripts chemical modi cation of eukaryotic, which has been identi ed to play critical roles on tumor metabolic reprogramming. However, the functions of m 6 A reading protein YTH N 6 -methyladenosine RNA binding protein 3 (YTHDF3) in osteosarcoma is still unclear. This research planed to investigate the bio-functions and mechanism in osteosarcoma tumorigenesis. Results indicated that YTHDF3 up-regulated in the osteosarcoma tissue samples and cells, and closely correlated to the poor prognosis of osteosarcoma patients. Functionally, gain and lossof-functional assays illustrated that YTHDF3 promoted the proliferation and aerobic glycolysis of osteosarcoma cells in vitro, and accelerated the tumor growth in vivo. Mechanistically, a m 6 A-modi ed PGK1 mRNA functioned as the target of YTHDF3, and YTHDF3 enhanced the PGK1 mRNA stability via m 6 A-dependent manner. In conclusion, these ndings indicated that YTHDF3 functioned as an oncogene in osteosarcoma tumorigenesis through m 6 A/PGK1 manner, providing a therapeutic strategy for human osteosarcoma.

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Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Cited by 7 publications

References 36 publications

Influence of Housing Temperature and Genetic Diversity on Allogeneic T Cell-Induced Tissue Damage in Mice

Influence of Housing Temperature and Genetic Diversity on Allogeneic T Cell-Induced Tissue Damage in Mice

Comprehensive mapping of immune perturbations associated with aplastic anemia

N6-methyladenosine reader YTHDF3 contributes to the aerobic glycolysis of osteosarcoma through stabilizing PGK1 stability

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