bims-maitce 2026-08-23 papers

Issue of 2026–08–23
four papers selected by
Andy E. Hogan, Maynooth University

Brain Behav Immun. 2026 Aug 21. pii: S0889-1591(26)00717-8. [Epub ahead of print] 106969

The MR1/MAIT cell axis has limited effects on the start of tau pathology in a mouse model of tauopathy.

Season K Wyatt-Johnson, Sujal Joshi, Maggie Blair, Jay M Desai, S M Mansour Haeryfar, Cristian A Lasagna-Reeves, Randy R Brutkiewicz.

Immunity impacts all aspects of Alzheimer's disease (AD) pathology. Previously, we found improved pathology and cognition in the amyloid-focused 5XFAD mouse model deficient in the innate immune cell axis consisting of the innate-like mucosal-associated invariant T (MAIT) cells and the MHC class I-like antigen-presenting molecule they recognize, MR1. However, little is known about how a lack of the MR1/MAIT cell axis impacts cognition and whether an increased abundance of MAIT cells impacts pathology and cognition in the tau-focused PS19 mouse model. We crossed PS19 mice onto an MR1 KO background, resulting in a lack of both MR1 and MAIT cells, and alternatively, onto MAITCAST mice, that have ∼7× more MAIT cells. Using immunofluorescent microscopy, flow cytometry, and cognitive tests including Barnes maze and Novel Object Recognition, we analyzed the impact of MAIT cell numbers on tau pathology. Although an elevation in MAIT cell frequency was found that expressed higher levels of CD69 in PS19 mice on the MAITCAST vs. wildtype background, overall MAIT cell numbers in the brain did not differ between these groups. Interestingly, increased MR1 expression was detected on microglia only in PS19 mice, whereas MR1 was higher in PS19 and PS19/MAITCAST mouse astrocytes. Increased MAIT cell numbers did not alter tau accumulation or cognitive performance, whereas the lack of the MR1/MAIT cell axis did not affect tau burden, but was associated with reduced neuronal density and impaired recognition memory. Together, these findings suggest that the MR1/MAIT cell axis does not substantially influence the early development of tau pathology.

Keywords: Alzheimer’s disease; Astrocytes; Innate immunity; Microglia; Tau

DOI: https://doi.org/10.1016/j.bbi.2026.106969

Proc Natl Acad Sci U S A. 2026 Aug 25. 123(34): e2617943123

Select intratumoral riboflavin-auxotrophic Enterococcus species enhance cell surface MR1 expression and MAIT TCR activation in lung cancer.

Pakhi Birla, Lansaol Yang, Wanting Shan, Sakura Minamisawa, Omkar Dhaygude, Haritha Manoj, Alex J Lee, Jacqueline Ferri, Ying Zheng, Andrew Northcutt, Hongni Fan, Hadley Beauregard, Zhen Zeng, Kellie N Smith, Fyza Y Shaikh, Cynthia L Sears, Drew M Pardoll, Franck Housseau.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells capable of MR1-dependent immune surveillance, but how intratumoral bacteria modulate MR1 expression in human lung tumors remains unclear. We studied intratumoral MAIT cells from paired single-cell RNA and TCR sequencing datasets of tumor-infiltrating CD3 T cells isolated from non-small cell lung cancer tumors in patients receiving neoadjuvant PD-1 blockade therapy. MAIT cells were subclustered to identify conventional MAIT-associated TCR clonotypes, which were then used to examine how bacterial exposure impacts cell-surface MR1 expression and downstream MAIT TCR activation. We found that select intratumoral Enterococcus species (spp.) did not directly activate MAIT cells but enhanced MR1-dependent MAIT activation in the presence of exogenous 5-OP-RU by increasing cell-surface MR1 expression on antigen-presenting cells including dendritic cells, B cells, and mononuclear phagocytes. This increase in MR1 cell surface expression is modulated through a posttranscriptional mechanism consistent with altered intracellular processing and trafficking of MR1. These findings reveal a role for tumor-associated bacteria in modulating MR1-dependent innate-like T cell activation and provide a basis for future studies examining whether this process influences response to immune checkpoint blockade.

Keywords: Enterococcus; MAIT; MR1; tumor microbiome

DOI: https://doi.org/10.1073/pnas.2617943123

Blood. 2026 Aug 18. pii: blood.2025032849. [Epub ahead of print]

Immune cell subsets that predict cytomegalovirus reactivation magnitude after haematopoietic stem cell transplantation.

Danya Yona Kaplan, Emily Blyth, Selmir Avdic, David J Gottlieb, Allison Abendroth, Lauren Stern, Barry Slobedman.

Haematopoietic stem cell transplantation (HSCT) is a curative-intent treatment for otherwise lethal haematological malignancies. The first 100 days post-transplant is a period of high risk for opportunistic infections, including reactivation of latent viruses, as the recipient's immune system reconstitutes. Human cytomegalovirus (HCMV) is the most frequent virus to reactivate post-HSCT, however, there are no simple and well validated biomarkers that predict HCMV reactivation and its subsequent course. In this study, we identified potential predictive immune signatures for HCMV reactivation occurrence and viral load magnitude. We developed a 21-parameter spectral cytometry antibody panel to characterise peripheral blood mononuclear cells (PBMCs) from adult allogeneic HSCT-recipients (n=25) at four timepoints over the course of HCMV reactivation, including before and at initial detection of HCMV DNAemia. Prior to HCMV reactivation, CD4+ T, Vδ2pos γδT and mucosal-associated invariant T (MAIT) cells from patients who would later reactivate HCMV exhibited CD69+ phenotypes. At the initial detection of HCMV reactivation, patients who went on to experience high-level HCMV DNAemia had lower CD45RO+CD27- CD8+ T-cell, and greater CD57+ Vδ2pos γδT and TIM-3+ CD4-CD8+ MAIT cell compartments than those with controlled infection. At later timepoints, MAIT cells acquired a chronically activated (CD38, granzyme B) and terminally exhausted (CD57, TIM-3) phenotype during high-level HCMV DNAemia. In summary, we present phenotypic distinctions in MAIT, γδT, conventional T and NK cells dependent on the subsequent trajectory of HCMV reactivation. We propose these cell subsets as predictive biomarkers for HCMV reactivation post-HSCT to inform clinical decision-making.

DOI: https://doi.org/10.1182/blood.2025032849

Phenomics. 2026 Apr;6(2): 137-149

Distinct T Cell Repertoires in Spinal Entheses and Synovial Fluids in Ankylosing Spondylitis.

Hongzi Zhu, Yulong Tang, Yuexin Yu, Qi Zhu, Li Jin, Jiucun Wang, Mark Hwang, Jing Liu.

Ankylosing spondylitis (AS) is a chronic inflammatory condition primarily impacting the spine and sacroiliac joints, driven by immune dysregulation. While T cells are known contributors to AS, the specific cellular and molecular changes within affected tissues, especially in the spine, remain to be fully elucidated. We conducted single-cell RNA (scRNA-seq) and T cell receptor (TCR) sequencing on synovial fluids and spinal ligament samples from AS patients, supplemented by public AS and healthy control data. The analysis identified nine T cell clusters, with CD8 + memory T cells enriched in spine ligaments (SL), while mucosal-associated invariant T lymphocytes (MAIT) cells and regulatory T lymphocytes (Tregs) were enriched in synovial fluids. Differential expression and pathway analyses revealed that senescence-related genes, such as calmodulin 1 (CALM1) and cyclin-dependent kinase inhibitor 1A (CDKN1A), were enriched in SL, suggesting the presence of senescent T cells, and cytotoxic genes, including natural killer cell granule protein 7 (NKG7), were enriched in synovial fluids. Furthermore, TCR repertoire analysis uncovered biased usage of T cell receptor gamma variable (TRGV) genes in SL and T cell receptor beta variable 9 (TRBV9) in synovial fluid, indicating tissue-specific clonal expansion. Lastly, peptide prediction identified potential human leukocyte antigen-B27 (HLA-B27)-presented peptides, highlighting their contribution to inflammation. Our study demonstrates a unique immune landscape in AS, characterized by differential clonal expansion in peripheral and axial joints. These findings underscore T cell-mediated immune responses in AS pathology, contributing to the understanding of the immunological mechanisms of AS and potential immune-focused therapies.
Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-025-00292-z.

Keywords: Ankylosing spondylitis; Single-cell T cell receptor sequencing; Spine ligament; Synovial fluid

DOI: https://doi.org/10.1007/s43657-025-00292-z