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Myeloid-derived suppressor cell and regulatory T cell frequencies in canine myasthenia gravis: A pilot study.

ABSTRACT: Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated autoimmune disease. Little is known about its cellular pathogenesis in dogs. This study provides the first preliminary assessment of the frequency of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of dogs with seropositive generalized MG. No alteration in frequency of either MDSCs or Tregs in dogs with MG was observed when compared to those in either seronegative dogs with diagnoses other than MG, or healthy dogs. A longitudinal study in three dogs with MG revealed no correlation between the relative numbers of either population and the clinical course of disease. Neither the frequency of MDSCs nor of Tregs showed a correlation with anti-AChR antibody titer in dogs with MG. These findings suggest that aberrations in the frequency of either immunosuppressive population do not occur in MG, but they need to be validated in large-scale prospective studies.

SUBMITTER: Wu Y

PROVIDER: S-EPMC7780263 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Myeloid-derived suppressor cell and regulatory T cell frequencies in canine myasthenia gravis: A pilot study.

Wu Ying Y Chang Yu-Mei YM Lawson Brandon S BS Galban Evelyn M EM Mittelman Neil S NS Benedicenti Leontine L Petesch Scott C SC Carroll Alicia B AB Punt Jennifer A JA Luo Jie J Garden Oliver A OA

Veterinary journal (London, England : 1997) 20201128

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated autoimmune disease. Little is known about its cellular pathogenesis in dogs. This study provides the first preliminary assessment of the frequency of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of dogs with seropositive generalized MG. No alteration in frequency of either MDSCs or Tregs in dogs with MG was observed when compared to those in either seronegative dogs with diagnoses oth ...[more]

PMID: 33375962

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Project description:Objective: This study was conducted to determine whether regulatory T cells (CD4+CD25+T, Tregs) show abnormal mitophagy as well as the function of Tregs in patients with myasthenia gravis (MG). Methods: CD4+T cells and CD4+CD25+Treg cells were obtained from 15 patients with MG (MG group) and 15 controls (N group). Tregs from the MG group were subjected to rapamycin-induced culture for 48 h (Rapa group) and 3-methyladenine-induced culture for 48 h (3-MA group). The levels of mitophagy in Tregs were then observed through electron and confocal microscopy. Expression of the autophagy-related protein LC3-II was detected by western blotting, and mitochondrial function in each group was evaluated by flow cytometry. Inhibition of Treg cell proliferation was detected by flow cytometry. Results: Mitophagy in the MG group was lower than that in the N group; it was higher in the Rapa group compared to that in the MG group and lowered in the 3-MA group than in the MG group. Expression of the autophagy-related protein LC3-II was lower in the MG group than in the N group, higher in the Rapa group than in the MG group, and lower in the 3-MA group than in the MG group. The mitochondrial membrane potential was lower in the MG group compared to that in the N group; it was higher in the Rapa group than in the MG group and lowered in the 3-MA group than in the MG group. Inhibition of Treg proliferation was lower in the MG group than in the N group; it was higher in the Rapa group than in the MG group and lowered in the 3-MA group than in the MG group. Conclusion: The decreased mitochondrial membrane potential and mitophagy in Tregs in the MG group may be related to a decreased inhibition of Treg proliferation. The mitochondrial membrane potential was increased after adding the autophagy agent Rapa to enhance mitophagy, and the proliferation inhibition function of Tregs was also enhanced. The autophagy agent 3-MA down-regulated mitophagy, which decreased the mitochondrial membrane potential and inhibitory effect of Tregs. These results reveal the possible cellular immune mechanism of Treg dysfunction in MG.

Project description:ObjectiveTo find out if the failure in immunotolerance of myasthenia gravis (MG) is a possible aspect of deduction in Breg cells and to characterize B cell subsets in MG.MethodsFlow cytometry detection and enzyme-linked immunosorbent assays in peripheral blood films of 10 MG patients and 10 healthy controls (HCs) were performed after isolation of B cells. The CD19+CD5+CD1d+ Breg cells percentages were measured to complement a B cell phenotype assay and frequencies of B cell subsets. The clinical outcome measures and immunological variables of patients with MG were compared with HCs.ResultsPatients with MG had relatively lowered percentages of CD19+CD5+CD1d+ Breg cells as compared to HCs. The production of interleukin (IL)-10 and transforming growth factor (TGF)-β1 was relatively lesser in patients with MG than HCs, which were linked with more severe of MG disease status according to Myasthenia Gravis Foundation of America (MGFA) clinical classification. The reduction of cytokine production was more significant for IL-10 than TGF-β1 when compared to HCs.ConclusionIt has been observed that the reduced number of B cells is able to produce IL-10 in MG patients but lesser than compared to HCs. The Bregs reduction mainly was regarded by the severity of disease status, which was highly significant and also by disease duration which was statistically significant as well. The findings of the measurement of B cell phenotype assay and frequencies of B cell subsets between MGs and HCs give us new ideas to develop B cell-mediated therapies of MG such as (1) isolated B cells of MGs could be cultured with steroids, e.g., dexamethasone in vitro to see if it induces the CD19+CD5+CD1d+ Breg cells, (2) it may observe whether induced CD19+CD5+CD1d+ Bregs have higher production of IL-10 and TGF-β1, as both are linked with disease severity, and (3) after completion in vitro steps, through further research in vivo to observe whether it improves the function of MG disease status.

Dataset Information

Myeloid-derived suppressor cell and regulatory T cell frequencies in canine myasthenia gravis: A pilot study.

Publications

Myeloid-derived suppressor cell and regulatory T cell frequencies in canine myasthenia gravis: A pilot study.

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