Adipose-derived stem cells were impaired in restricting CD4T cell proliferation and polarization in type 2 diabetic ApoE mouse.

BACKGROUND

Atherosclerosis (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 CD4T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4T cells as well. Whether T2DM ADSCs are impaired in antagonizing CD4T cell proliferation and polarization remains unclear.

METHODS

We constructed type 2 diabetic ApoE mouse models and tested infiltration and subgroups of CD4T 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.

RESULTS

CD4T cells performed a more pro-inflammatory phenotype in adipose tissue in T2DM ApoE mice in vivo. Restriction to CD4T 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.

CONCLUSION

CD4T cell infiltration and pro-inflammatory polarization exist in adipose tissue in type 2 diabetic ApoE mice. T2DM ADSCs had impaired function in restricting CD4T lymphocyte proliferation and pro-inflammatory polarization due to immune phenotypic changes.