bims-maitce 2026-06-07 papers

Issue of 2026–06–07
six papers selected by
Andy E. Hogan, Maynooth University

Sci Signal. 2026 Jun 02. 19(940): eaec6992

Environmental regulation of mucosal-associated invariant T cells: Adding food for thought.

Eimear K Ryan, Linda V Sinclair, Andrew E Hogan.

Mucosal-associated invariant T (MAIT) cells are a population of innate-like, unconventional T cells characterized by the expression of a semi-invariant, non-MHC-restricted T cell receptor (TCR), which play an important role in mediating innate immune responses to bacterial and viral pathogens. Emerging research continues to describe the many environmental signals that influence the types of responses elicited downstream of MAIT cell activation. In this Review, we highlight five key factors that determine the metabolic and functional responses of MAIT cells, including TCR engagement, costimulation, chemokine signaling, cytokine stimulation, and nutrient availability. We further define the importance of optimal nutrient availability as "signal 5" in promoting MAIT cell fitness and in governing their capacity to respond appropriately to challenge. In understanding the ways in which MAIT cells are influenced by their microenvironment, we can continue to identify the potential factors that drive dysregulated responses in hostile circumstances, enabling restoration of their protective nature in the context of infection or in the tumor microenvironment.

DOI: https://doi.org/10.1126/scisignal.aec6992

Mult Scler. 2026 Jun 01. 13524585261447695

Microbiome-derived metabolites from vitamin B2 and B9 pathways modulate MAIT cells from multiple sclerosis patients.

Jorge Correale, Mariano Marrodan, Maria A Piedrabuena, Karthik Soman, Mauricio F Farez, Sergio E Baranzini.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells recognize microbial vitamin B2 and B9 metabolites via MR1 and have been implicated in multiple sclerosis (MS). How patient-specific gut microbiota shape human MAIT-cell pathogenicity at the clonal level remains unknown.
MATERIAL AND METHODS: We generated 62 MAIT-cell clones from relapsing-remitting multiple sclerosis (RRMS) patients and 50 from healthy controls (HCs). Clones were stimulated with riboflavin- or folate-pathway metabolites, paraformaldehyde-fixed patient-matched gut bacterial isolates, or interleukin (IL)-12/IL-18. Activation markers, cytokine secretion, cytotoxicity, and competitive MR1-ligand inhibition were assessed. Intestinal permeability was evaluated using I-FABP, LBP, GLP-2, and fecal α-1-antitrypsin.
RESULTS: MS-derived MAIT clones showed markedly enhanced activation, increased interferon-gamma (IFN-γ), IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion, and greater cytotoxicity compared with HCs when stimulated with riboflavin-producing taxa isolated from the same patients. Importantly, several responses diverged from predictions based on murine models and genomic inference, including mixed cytokine profiles and graded competitive inhibition by folate-derived ligands. These findings highlight species-specific differences in MR1 ligand handling and MAIT-cell activation. Activation required uptake of intact bacteria and acid-dependent MR1 loading. MS patients exhibited significant intestinal barrier dysfunction, linking dysbiosis to systemic MAIT-cell hyperactivation.
CONCLUSION: At clonal resolution, this study demonstrates that patient-specific microbial metabolism, MR1-ligand competition, and epithelial barrier disruption cooperate to amplify MAIT-cell pathogenicity in MS, revealing human-specific mechanisms not predicted by animal models.

Keywords: MAIT cells; cytokines; cytotoxicity; intestinal permeability; microbiome; multiple sclerosis

DOI: https://doi.org/10.1177/13524585261447695

Cell Immunol. 2026 May 29. pii: S0008-8749(26)00056-0. [Epub ahead of print]426 105116

Deficit in blood MAIT cells, altered cytokines and T cell dynamics in patients with coronary artery disease.

Dimitrios Stavridis, Max Wacker, Rauf Safarov, Nicola Testa, George Awad, Sam Varghese, Katrin Borucki, Jens Wippermann, Priya Veluswamy.

OBJECTIVES: Coronary artery disease (CAD) is a chronic inflammatory disorder characterized by immune dysregulation and a higher risk of viral infections. Among the immune cells involved, mucosal-associated invariant T (MAIT) cells participate in antimicrobial defense and tissue repair, yet their contribution to CAD has not been clearly defined.
METHODS: Peripheral blood mononuclear cells and plasma were obtained from patients with CAD and from healthy controls. MAIT cell subsets, conventional T cells, and the SARS-CoV-2 receptors ACE2 and CD147 were analyzed by flow cytometry. Cytokines were quantified using ELISA. Additional in-vitro assays were performed to test whether recombinant SARS-CoV-2 spike proteins could influence cell apoptosis or proliferation.
RESULTS: The number of circulating MAIT cells was markedly reduced in CAD, most notably within the CD8+ population. In contrast, CD4+ MAIT cells were relatively increased but expressed less CCR5 intensities, suggesting limited migratory ability. Plasma IL-7 concentrations were lower in CAD, while IL-18 and IFN-α2 were higher. These findings indicate a disturbed cytokine environment, especially for MAIT cell activation. CAD samples also showed more CD4+PD-1+ and fewer CD8+CD69+ T cells, pointing toward an exhausted phenotype. IL-18 levels correlated negatively with left-ventricular ejection fraction. Expression of ACE2 and CD147 was similar between groups, and spike-protein exposure did not trigger significant apoptosis or proliferation in vitro.
CONCLUSION: CAD is associated with loss and functional alteration of MAIT cells, cytokine imbalance, and T-cell exhaustion. Together, these immune changes may weaken antiviral defense mechanisms in the context of viral infections, such as the SARS-CoV-2 infection.

Keywords: Coronary artery disease; MAIT cells; MAIT-associated cytokines; SARS-CoV-2 spike proteins; T cell exhaustion

DOI: https://doi.org/10.1016/j.cellimm.2026.105116

J Inflamm Res. 2026 ;19 570529

MAIT Cells Maintain Intestinal Homeostasis Through IL-22 in an Experimental Colitis.

Yanan Peng, Chunlan Zheng, Youwei Wang, Fengxing Huang, Yu Shao, Lan Liu, Qiu Zhao.

Objective: Mucosa-associated invariant T (MAIT) cells are a unique subset of innate-like lymphocytes abundant in the gastrointestinal tract, yet their role in maintaining intestinal homeostasis remains incompletely understood. We investigated how MAIT cells contribute to epithelial barrier integrity and the molecular mechanisms underlying this process during experimental colitis.
Methods: Acute colitis was induced by dextran sulfate sodium (DSS) in wild-type (WT) and MR1-deficient (MR1-/-) mice. Disease severity was quantified via weight loss, colon length, and histopathology. Barrier function was assessed by FITC-dextran permeability and expression of tight junction proteins (ZO-1 and Claudin-1). Single-cell RNA sequencing (scRNA-seq) was employed to identify MAIT-cell- associated mediators, followed by rescue experiments with recombinant IL-22 or CCL2.
Results: MAIT cells accumulated in the inflamed colon and displayed a tissue-specific activated phenotype during DSS-induced colitis. MR1-/- mice developed more severe colitis than WT mice, with aggravated mucosal injury, increased inflammatory cytokine production, disrupted tight junction expression, enhanced intestinal permeability, and increased bacterial translocation. MAIT cell deficiency was associated with markedly reduced colonic IL-22 expression and impaired IL-22 production across multiple immune populations, including Th22 cells, Th17 cells, ILC3s, and CD4⁺ T cells. Recombinant IL-22 partially alleviated colitis and improved barrier-associated protein expression, indicating that IL-22 is an important downstream mediator of MAIT cell-dependent protection. Mechanistically, single-cell RNA sequencing identified CCL2 as a MAIT-associated soluble factor induced during colitis. In vivo CCL2 supplementation restored AHR/CYP1A1 expression, enhanced IL-22 production in Th22 and other lymphocyte subsets, and ameliorated epithelial barrier damage and disease severity in MR1-/- mice.
Conclusion: Our study identifies a novel MAIT-CCL2-AHR-IL-22 regulatory axis that that contributes to epithelial barrier protection during acute experimental colitis. MAIT cells appear to act not only as effector cells but also as upstream coordinators of IL-22-dependent mucosal repair, providing a mechanistic basis for targeting this pathway in intestinal inflammatory disease.

Keywords: CCL2; IL-22; MAIT cell; acute experimental colitis; inflammatory bowel disease; intestinal barrier

DOI: https://doi.org/10.2147/JIR.S570529

Hum Reprod. 2026 Jun 05. pii: deag090. [Epub ahead of print]

Deep immune profiling of endometrial and peripheral blood cells in endometriosis.

A Kisovar, M Buttenschoen, Q Obrigewitch, K Powell, P Klenerman, K Zondervan, C M Becker, I E Granne, J H Southcombe.

STUDY QUESTION: How is endometrial and systemic immunity modulated throughout the menstrual cycle and are there changes in women with endometriosis?
SUMMARY ANSWER: Endometriosis is associated with reduced endometrial early natural killer (NK) cells and increased mucosal-associated invariant T (MAIT)-like CD8+ T cells, with cyclical variation.
WHAT IS KNOWN ALREADY: The endometrial mucosa contains innate and adaptive immune cells that fluctuate across the menstrual cycle. Immune dysregulation is found in endometriosis, however few studies have broadly assessed endometrial immune single-cell proteome phenotypes.
STUDY DESIGN, SIZE, DURATION: This observational cross-sectional immune phenotyping study included 40 participants (28 with surgically confirmed endometriosis and 12 controls).
PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial and peripheral blood samples were analysed by spectral flow cytometry using a 36-parameter immune phenotyping panel and a 13-parameter MAIT-specific panel. Totals of 1 950 292 circulating and 1 023 215 endometrial immune cells were profiled. Full-thickness uterine biopsies (n = 3) underwent multiplex immunohistochemical imaging to assess spatial organization across the menstrual cycle.
MAIN RESULTS AND THE ROLE OF CHANCE: Compared with controls, patients with endometriosis exhibited decreased endometrial early NK cells (P.adj = 0.006, log2FC = -1.369) and increased MAIT-like CD8+ T cells (CD161+CD8+CD3+) (P.adj = 0.033, log2FC = 1.415). The MAIT cells (CD161+Va7.2+CD3+) peaked during ovulation and the implantation window (P.adj < 0.05). Peripheral immunity also showed cyclical variation with increased early NK cells (P.adj = 0.001, log2FC = 1.052) and decreased effector CD4 T (P.adj = 0.002/log2FC = -2.010) and effector CD8 T cells (P.adj = 0.002, log2FC = -1.180) in the endometriosis group.
LIMITATIONS, REASONS FOR CAUTION: The cytometric panel design was biased towards acquired immunity, and the endometriosis patient sample size prevented subtype analysis.
WIDER IMPLICATIONS OF THE FINDINGS: MAIT cell dysregulation represents a novel feature of endometriosis, potentially contributing to subfertility and providing new avenues for therapeutic development.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Nuffield Department of Women's and Reproductive Health, University of Oxford, and also supported from the University of Oxford Medical Sciences HIDI Internal Fund Award (0010398), Academy of Medical Science Award (SBF007\100078) and, British Society for Immunology Career Enhancing Grant. C.M.B. has a consultancy role with ObsEva, Theramex, Roche Diagnostics, Sumitovant, Gedeon Richter, Gesyntha, and they have Research Grants from Bayer, Gesyntha, and Serac Life Services. K.Z. is a Board member (non-remunerated) of the World Endometriosis Research Foundation. She has consultancy status with Roche Diagnostics and Gedeon Richter. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
TRIAL REGISTRATION NUMBER: N/A.

Keywords: endometriosis; endometrium; immunity; menstrual cycle; spectral flow cytometry

DOI: https://doi.org/10.1093/humrep/deag090