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Human adipose tissue-derived mesenchymal stem cells in Parkinson's disease:Inhibit T helper 17 cell differentiation and regulate immune balance towards a regulatory T cell phenotype

· 2020-01-31

DOI: 10.21203/rs.2.21813/v2

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Research overview

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Abstract Parkinson's disease (PD), known as a neurodegenerative disorder, shows typical pathology of neuroinflammation, which might be the result of the imbalance between regulatory T cells (Treg) and T helper 17 (Th17) cells. The present study aimed to investigate the modulating effect of Ad-MSCs on peripheral blood mononuclear cells (PBMCs) derived from PD patients. CD4 + peripheral blood T cells were isolated and co-cultured with Ad-MSCs at a ratio of 4:1 under Th17 or Treg polarizing conditions, respectively, for 4 days. Our results showed that Ad-MSCs specifically inhibited the differentiation of IL-17-producing CD4 + T cells collected from PBMCs of PD patients evidenced by the decreased expression of RORγt- the key transcription factor for Th17 cells, IL-6R, and IL-23R. In the meantime, Ad-MSCs and induced a functional CD4 + CD25 + Foxp3 + T regulatory cell phenotype evidenced by the secretion of IL-10. Furthermore, levels of LIF protein and its receptor mRNA were significantly increased under both polarizing conditions. These findings suggest that the regulation of the Th17/Treg balance by Ad-MSCs was correlated with the increase in LIF secretion. Therefore, Ad-MSCs are an important player in ­modulating inflammatory responses and a potential therapeutics for PD patients.

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