Ming-Hao Liu1, Ya Li1, Lu Han2, Yao-Yuan Zhang1, Di Wang1, Zhi-Hao Wang3, Hui-Min Zhou1, Ming Song1, Yi-Hui Li1, Meng-Xiong Tang4, Wei Zhang1, Ming Zhong5. 1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. 2. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Department of General Practice, Qilu Hospital of Shandong University, Ji'nan, China. 3. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Department of Geriatrics, Qilu Hospital of Shandong University, Ji'nan, China. 4. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Department of Emergency, Qilu Hospital of Shandong University, Ji'nan, China. 5. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. Electronic address: zhongmingzm@gmail.com.
Abstract
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 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. METHODS: We 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. RESULTS: CD4+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. CONCLUSION: CD4+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.
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 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. METHODS: We constructed type 2 diabeticApoE-/- 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. RESULTS:CD4+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. CONCLUSION:CD4+T cell infiltration and pro-inflammatory polarization exist in adipose tissue in type 2 diabeticApoE-/- mice. T2DM ADSCs had impaired function in restricting CD4+T lymphocyte proliferation and pro-inflammatory polarization due to immune phenotypic changes.