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Mol Immunol. 2017 Jul;87:152-160. doi: 10.1016/j.molimm.2017.03.020. Epub 2017 Apr 25.

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

Author information

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.

KEYWORDS:

Adipose inflammation; Adipose-derived stem cell; CD4(+)T cell; Pro-inflammatory polarization; Proliferation

PMID:
28445787
DOI:
10.1016/j.molimm.2017.03.020
[Indexed for MEDLINE]

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