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Poor Collateralization in T2DM: Role of SLC4A10+ MAIT Cells
Shuai Chen1,2, Ke Huang1,2, Ting Zhang3
1Department of Cardiovascular Medicine, Rui Jin Hospital (S.C., K.H., Z.-M.W., F.-F.L., Y.M., X.-L.W., J.-M.L., X.-R.W., Q.-J.C., Y.S., X.-Q.W., R.-S.Y., W.-J.L., L.L., Y.D., F.-H.D.), Shanghai Jiao Tong University School of Medicine, P.R. China.
Arteriosclerosis, Thrombosis, and Vascular Biology
|August 14, 2025
Summary
Mucosal-associated invariant T (MAIT) cells are elevated in type 2 diabetes patients with poor blood vessel collateralization. Inhibiting MAIT cells improved blood vessel formation, suggesting MAIT cell levels could predict or treat this complication.
Area of Science:
- Immunology
- Cardiovascular Science
- Metabolic Disease Research
Background:
- Type 2 diabetes (T2D) is linked to poor blood vessel collateralization, increasing cardiovascular risks like heart attack and heart failure.
- Chronic total occlusion in T2D patients exacerbates these risks due to inadequate collateral circulation.
- Understanding immune cell roles in T2D-related collateralization is crucial for managing cardiovascular complications.
Purpose of the Study:
- To investigate immune cell dynamics in T2D patients with chronic total occlusion and their impact on collateralization.
- To identify specific immune cell types associated with good versus poor collateralization.
- To explore the mechanisms by which immune cells influence angiogenesis in diabetes.
Main Methods:
- Single-cell RNA sequencing of peripheral blood mononuclear cells from T2D patients with good/poor collateralization.
- Coculture experiments and induced ischemic hindlimb/myocardial models in diabetic mice.
- Validation in an independent patient cohort.
Main Results:
- Elevated mucosal-associated invariant T (MAIT) cells were identified in T2D patients with poor collateralization.
- MAIT cell inhibition improved angiogenesis in diabetic mice with ischemic conditions.
- MAIT cell-derived CCL3L1 promoted pro-inflammatory macrophage polarization via CCR5.
- Elevated MAIT cell levels were confirmed as an independent risk factor for poor collateralization.
Conclusions:
- MAIT cells play a critical role in regulating collateralization in T2D patients with chronic total occlusion.
- Circulating MAIT cell levels may serve as a potential biomarker for predicting and intervening in poor collateralization.
- Targeting MAIT cells could offer a novel therapeutic strategy for improving cardiovascular outcomes in T2D.
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