bims-maitce 2025-08-17 papers

Issue of 2025–08–17
two papers selected by
Andy E. Hogan, Maynooth University

bioRxiv. 2025 Jul 20. pii: 2025.07.20.665728. [Epub ahead of print]

The antigen presenting molecule MR1 binds riboflavin catabolites.

Mohamed R Abdelaal, Jieru Deng, Mitchell P McInerney, Emi Ito, Anthony W Purcell, Sho Yamasaki, Jose Villadangos, Hamish E G McWilliam, Nicholas A Gherardin, Jamie Rossjohn, Wael Awad.

Major histocompatibility-complex (MHC) class I-related (MR1) protein presents vitamin B based antigens to Mucosal-Associated Invariant T (MAIT) cells. While microbial riboflavin precursors are well documented MR1 ligands, it is unclear whether host-generated riboflavin catabolites influence MR1-mediated immunity. Here, we report that riboflavin catabolites, including 10-formylmethylflavin (FMF), lumichrome, lumiflavin and alloxazine bind to MR1 with moderate affinity, while riboflavin itself binds weakly. In contrast to the microbial riboflavin antigens which increase MR1 cell surface expression, the riboflavin catabolites moderately reduced cell surface levels of MR1 by stabilizing and retaining MR1 in the endoplasmic reticulum (ER). The riboflavin catabolites appeared to bind to the intracellular MR1 and inhibit MR1 exit from the ER. These riboflavin catabolites also weakly competed with Vit B based Ags for MR1 binding, thereby inhibiting MAIT cell activation. The crystal structures of MR1 complexed with riboflavin, FMF, lumichrome and lumiflavin, show binding of these three-ringed ligands in the A'-pocket of MR1. The crystal structure of MR1-lumichrome revealed that lumichrome formed a covalent "flavin bond" with MR1-Lys43 differing from the typical Schiff-base bond of MR1-Lys43-Ag complexes. Collectively, we identified three ring isoalloxazines that can bind MR1 and downregulate cell surface expression levels, suggesting a potential role in dampening MAIT cell immunity.

DOI: https://doi.org/10.1101/2025.07.20.665728

Arterioscler Thromb Vasc Biol. 2025 Aug 14.

Poor Collateralization in T2DM: Role of SLC4A10+ MAIT Cells.

Shuai Chen, Ke Huang, Ting Zhang, Zhi-Ming Wu, Fei-Fei Li, Yipaerguli Maimati, Xue-Lian Wang, Jing-Meng Liu, Xin-Rui Wu, Qiu-Jing Chen, Ying Shen, Xiao-Qun Wang, Ruo-Sen Yuan, Wen-Jia Li, Lin Lu, Yang Dai, Feng-Hua Ding.

BACKGROUND: Type 2 diabetes is strongly associated with impaired collateralization, which increases the risk of cardiovascular complications, such as myocardial infarction and heart failure. This study explored the immune cell dynamics in patients with type 2 diabetes with chronic total occlusion and their impact on collateralization.
METHODS: Peripheral blood mononuclear cells were extracted from patients with type 2 diabetes with chronic total occlusion, exhibiting either good or poor collateralization. Single-cell RNA sequencing was conducted to profile the quantitative and transcriptomic dynamics of immune cells in these 2 groups. Moreover, coculture experiments were executed, and ischemic models of the hindlimb and myocardium were induced in diabetic mice to corroborate the single-cell RNA sequencing findings. Additional validation was attained by conducting an analysis on a separate cohort of patients.
RESULTS: Single-cell RNA sequencing of peripheral blood mononuclear cells identified elevated levels of mucosal-associated invariant T (MAIT) cells in patients with poor collateralization. In diabetic mice, inhibition of MAIT cell activation significantly improved angiogenesis under ischemic conditions. In vitro, MAIT cell-derived CCL3L1 drove macrophage polarization toward a proinflammatory phenotype through CCR5 interaction. Furthermore, an independent patient cohort confirmed that elevated MAIT cell levels represent an independent risk factor for poor collateralization.
CONCLUSIONS: These findings highlight the critical role of MAIT cells in regulating collateralization in type 2 diabetes chronic total occlusion patients and propose circulating MAIT cell levels as a potential biomarker for predicting and intervening in poor collateralization.

Keywords: cardiovascular diseases; coronary artery disease; diabetes mellitus, type 2; heart failure; myocardial infarction

DOI: https://doi.org/10.1161/ATVBAHA.125.322718