Adipose-derived stem cells were impaired in restricting CD4+T cell proliferation and polarization in type 2 diabetic ApoE−/− mouse

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Ming-hao Liu, Ya Li, Lu Han, Yao-yuan Zhang, Di Wang, Zhi-hao Wang, Hui-min Zhou, Ming Song, Yi-hui Li, Meng-xiong Tang, Wei Zhang, Ming Zhong
BackgroundAtherosclerosis (AS) is the most common and serious complication of type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic inflammation rather than hyperglycemia. Adipose tissue is the major source of systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4⁺T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4⁺T cells as well. Whether T2DM ADSCs are impaired in antagonizing CD4⁺T cell proliferation and polarization remains unclear.MethodsWe constructed type 2 diabetic ApoE^−/− mouse models and tested infiltration and subgroups of CD4⁺T cell in stromal-vascular fraction (SVF) in vivo. Normal/T2DM ADSCs and normal splenocytes with or without CD4 sorting were separated and co-cultured at different scales ex vivo. Immune phenotypes of pro- and anti-inflammation of ADSCs were also investigated. Flow cytometry (FCM) and ELISA were applied in the experiments above.ResultsCD4⁺T cells performed a more pro-inflammatory phenotype in adipose tissue in T2DM ApoE^−/− mice in vivo. Restriction to CD4⁺T cell proliferation and polarization was manifested obviously weakened after co-cultured with T2DM ADSCs ex vivo. No obvious distinctions were found in morphology and growth type of both ADSCs. However, T2DM ADSCs acquired a pro-inflammatory immune phenotype, with secreting less PGE2 and expressing higher MHC-II and co-stimulatory molecules (CD40, CD80). Normal ADSCs could also obtain the phenotypic change after cultured with T2DM SVF supernatant.ConclusionCD4⁺T cell infiltration and pro-inflammatory polarization exist in adipose tissue in type 2 diabetic ApoE^−/− mice. T2DM ADSCs had impaired function in restricting CD4⁺T lymphocyte proliferation and pro-inflammatory polarization due to immune phenotypic changes.



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