bims-maitce 2026-05-24 papers

Issue of 2026–05–24
five papers selected by
Andy E. Hogan, Maynooth University

Int J Genomics. 2026 ;2026 5460709

Single-Cell RNA Sequencing Reveals Dynamic Expression Patterns of MAIT Cells and Macrophage Subpopulations in Myocardial Injury Model.

Haofei Kang, Junjie Wang, Renjie Ruan, Yudan Wen, Bingru Chen, Meixiang Wu, Yongguang Wang, Yunrui Zhang.

Background: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes involved in immune surveillance and tissue homeostasis. Yet, their transcriptional dynamics and functional crosstalk with macrophages at the time of myocardial injury are incompletely defined.
Methods: We used two publicly available single-cell RNA sequencing (scRNA-seq) datasets from a murine ischemia-reperfusion myocardial injury model (GSM8252253 and GSM8252254). Following quality control and clustering, immune cell composition, cytokine expression patterns, and macrophage polarization states were systematically characterized. Concurrently, in vitro coculture experiments validated the MR1-dependent regulatory effects of 5-OP-RU-activated MAIT cells on macrophage cytokine expression.
Results: Single-cell analysis showed significant immune remodeling on Day 7 post-injury, with a relative expansion of B cells and depletion of macrophages compared to controls. UMAP-based feature mapping revealed that expression of Tnf was significantly restricted to myeloid compartments (especially monocytes), whereas Il10 exhibited a diffuse pattern across immune subsets. MAIT cells exhibited increased expression of signature genes such as ZBTB16 and KLRB1 consistent with activation-associated transcriptional reprogramming after damage. Macrophage populations exhibited heterogeneous polarization states, with limited TNF-α/IL-10 coexpression and overall low Il10 abundance in vivo. Functional validation showed that 5-OP-RU-activated MAIT cells significantly suppressed TNF-α while enhancing IL-10 expression in macrophages, and these effects were largely reversed by MR1 blockade.
Conclusions: Our findings reveal dynamic immune cell remodeling and transcriptional adaptation of MAIT cells during myocardial injury. The predominance of Tnf-driven myeloid signaling and the MR1-dependent anti-inflammatory modulation of macrophages by activated MAIT cells highlight a potential regulatory axis in cardiac inflammation. These results provide mechanistic insight into MAIT-macrophage interactions and suggest potential immunomodulatory targets for myocardial injury intervention.

Keywords: IL-10; MAIT cells; MR1; TNF-α; immune remodeling; macrophage polarization; myocardial injury; single-cell RNA sequencing

DOI: https://doi.org/10.1155/ijog/5460709

Commun Biol. 2026 May 20.

The PGD2/DP2 axis promotes pro-inflammatory responses but attenuates an antigen-presenting role of human basophils.

Jian Luo, Wentao Chen, Martin J Lett, Simin Yu, Wei Luo, Emma Coakley, Shamsah Kazani, Eric A Shikatani, Timothy S C Hinks, David A Sandham, Ian D Pavord, Paul Klenerman, Luzheng Xue.

Basophils are distinct blood leucocytes that express immunoglobulin E (IgE) receptor FcεR1 and can be activated by IgE. Their roles in asthma, particularly IgE-independent effects, remain incompletely understood. Human basophils highly express the prostaglandin D2 (PGD2) receptor 2 (DP2; also known as chemoattractant receptor homologous molecule expressed on Th2 cells, CRTH2). Here, we explore the PGD2/DP2 axis as an alternative pathway for basophil activation. Basophils are enriched in patients with severe eosinophilic asthma, correlating with eosinophil counts but not IgE levels. PGD2/DP2 stimulation promotes basophil recruitment, activation, and the production of histamine, leukotrienes, and type 2 cytokines. RNA sequencing and further in vitro experiments reveal that, although PGD2 and IgE share some signalling pathways and functions, they induce distinct gene transcriptional signatures. Interestingly, PGD2 downregulates major histocompatibility complex class I-related gene protein (MR1) and attenuates basophil antigen-presentation to mucosal-associated invariant T (MAIT) cells, leading to reduced IFN-γ production. These findings highlight the PGD2/DP2/basophil axis as a contributor to asthma, particularly in IgE-low conditions, and suggest it as a potential therapeutic target for related diseases.

DOI: https://doi.org/10.1038/s42003-026-10286-w

Gut. 2026 May 19. pii: gutjnl-2025-337343. [Epub ahead of print]

MAIT cell enrichment in Lynch syndrome is associated with immune surveillance and colorectal cancer risk.

Hairu Yang, Michaela Dungan, Bhoomi Madhu, Keely Beyries, Xin Wang, Robert Kilpatrick, Baron Chen, Sangmi Oh, Marissa Berkowitz, David Smith, Chaoting Zhou, Sergei B Koralov, Jordan Axelrad, Christopher J Lengner, Nicole Belle, Meenakshi Bewtra, Bryson W Katona, Ken Cadwell.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and results from pathogenic germline variants affecting mismatch repair. The tissue microenvironment that contributes to this elevated risk of CRC is poorly characterised particularly during the early precancerous stages.
OBJECTIVE: To define features of the colonic microenvironment that distinguish LS carriers with and without a history of CRC from one another and from the general population.
DESIGN: We applied Expanded Cellular Indexing of Transcriptomes and Epitopes by sequencing, a multimodal single-cell platform, to profile tumour-free colonic cellular composition and transcriptome of LS carriers with and without a history of CRC compared with general population controls. We used flow cytometry, histology and mouse modelling to validate key observations.
RESULTS: We observed widespread remodelling in LS that included striking expansion of epithelial stem and progenitor cells, loss of fibroblast populations and changes in lymphocyte subsets. Although clonally expanded and terminally exhausted CD8 T cells were more prominent in individuals with a history of CRC, LS carriers without CRC displayed enrichment of cytotoxic mucosal-associated invariant T (MAIT) cells associated with CCL20 expression in epithelial progenitors, validated by orthogonal techniques including demonstration of a protective function in a murine model of CRC.
CONCLUSIONS: These findings define key features of the LS colonic microenvironment and suggest that MAIT cell enrichment contributes to immune surveillance against CRC, offering new insights into disease penetrance, risk stratification and prevention.

Keywords: CANCER IMMUNOBIOLOGY; COLORECTAL CANCER

DOI: https://doi.org/10.1136/gutjnl-2025-337343

Thorax. 2026 May 20. pii: thorax-2024-222059. [Epub ahead of print]

Breaking with convention: the role of lymphocytes in IPF.

Kelly L Short, Donal O'Malley, Gerard Hoyne, Marc Hertz, Albert Agro, Vipin Kumar, Cecilia M Prêle, Adam J Byrne.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease characterised by excessive extracellular matrix deposition, leading to respiratory failure. While the exact aetiology of IPF remains unclear, growing evidence suggests that immune dysregulation plays a pivotal role in its pathogenesis. Recent research highlights the involvement of conventional (CD4+, CD8+ T cells as well as B cells), and unconventional T cell subsets, including natural killer T cells and mucosal-associated invariant T cells in fibrotic lung disease. Unconventional T cell subsets are known for their rapid response to stress signals, antigen-independent activation and involvement in tissue homeostasis and repair. Their potential to modulate fibrosis through interactions with fibroblasts, macrophages and epithelial cells positions them as key players in lung injury and repair mechanisms.
METHODS: This review explores the current knowledge of both conventional and unconventional lymphocytes in IPF, examining their contributions to fibrosis development and their potential as therapeutic targets.
CONCLUSIONS: By elucidating their functions and interactions within the lung microenvironment, we provide insights into novel immunomodulatory strategies for IPF treatment.

Keywords: Idiopathic pulmonary fibrosis

DOI: https://doi.org/10.1136/thorax-2024-222059

J Chromatogr B Analyt Technol Biomed Life Sci. 2026 May 14. pii: S1570-0232(26)00204-7. [Epub ahead of print]1280 125115

Development of HPLC protocol for isolation of MHC class I related protein 1 (MR1) antigens from mycobacteria.

Nurudeen Oketade, Kieran Broder, Aneta Worley, Gwendolyn M Swarbrick, Carolina Mehaffy, Deborah A Lewinsohn, David M Lewinsohn, Karen M Dobos.

Major histocompatibility class I related protein 1 (MR1) restricted T-cells (MR1T cells) play an important role during Mycobacterium tuberculosis (Mtb) infection. Unlike conventional T-cells that recognize peptides, MR1T cells recognize metabolic antigens. Studies to better understand the role of MR1T cells during Mtb infection depend on the identification of their cognate metabolic antigens. Although we and others have shown the importance of the riboflavin biosynthetic pathway for the production of these MR1 antigens, the identity of these metabolites from Mtb is yet to be determined. The identification of these antigens has been hampered by their relatively low abundance and the complex nature of the metabolome of Mtb. Also, Mtb produces several metabolites that competitively inhibit and antagonize MR1 antigens. Therefore, the discovery of MR1 antigens from Mtb poses a significant challenge. To overcome this challenge, we developed a high-performance liquid chromatography (HPLC) workflow to enrich for MR1 antigens from Mtb. First, by comparing multiple extraction approaches, we found that mechanical disruption by bead beating combined with an acetonitrile:methanol:water solvent system (2,2,1, v/v/v) provided the most efficient and reproducible extraction of MR1 ligands from mycobacteria. Finally, we optimized key chromatographic parameters, including mobile-phase pH, injection solvent, and column chemistry, to ensure stable and reproducible enrichment of MR1 ligands from mycobacterial extracts. Optimal separation was achieved using a HILIC column (BEH Amide) at pH 6, with a polar organic solvent system used for both extraction and sample injection. Under these conditions, we successfully enriched MR1 antigens from Mtb. This study serves as the first comprehensive report describing an enrichment workflow for MR1 antigens from mycobacteria. Further work will focus on identifying these ligands by integrating MR1 tetramer-based loading with LC-MS/MS analysis of the enriched fractions. Collectively, this method provides a practical platform to facilitate discovery of novel MR1 antigens from Mtb and other mycobacterial species.

Keywords: Antigens; Flavins; HILIC; HPLC; MR1; Mucosal associated invariant T-cell (MAIT); Mycobacteria; Tuberculosis

DOI: https://doi.org/10.1016/j.jchromb.2026.125115