bims-maitce 2026-08-16 papers

bims-maitce

Biomed News

on MAIT cells

Issue of 2026–08–16
nine papers selected by
Andy E. Hogan, Maynooth University

Rapid glycolytic metabolism underpins mucosal-associated invariant T cell functional responses to innate cytokines.
The MHC-I related protein 1 MR1 can bind host purine catabolites.
A Stable Isopterin Mimic of a Potent Bacterial Stimulant of T Cells.
Eltrombopag-associated remodeling of the MAIT, MR1+ and γδ T cells in pediatric immune thrombocytopenia.
Unconventional T cells in urological cancers: catch them if you can.
Characterization of Peripheral Blood Immune Cell Features in SSA/SSB Double‑Positive Primary Sjögren's Disease Based on Single‑Cell RNA Sequencing.
In situ programming of unconventional T cells.
Single-cell Profiling of Lymphoid and Myeloid Compartments Reveals Coordinated Immune Dysregulation and Enhanced Monocyte-centric Intercellular Communication in Relapsing Polychondritis.
MAIT cells are associated with eosinophil presence and activation in the inflamed tissue of patients with eosinophilic esophagitis.

J Immunol. 2026 Aug 04. pii: vkag212. [Epub ahead of print]215(8):

Rapid glycolytic metabolism underpins mucosal-associated invariant T cell functional responses to innate cytokines.

Eimear K Ryan, Benjamin J Jenkins, Ronan Bergin, Rafael E Salazar, Cian Davis, Nidhi Kedia-Mehta, Ali Amini, Lucy C Garner, Ciara Flynn, Sinéad Ryan, Iain Perry, Joanne C Masterson, Helen Heneghan, Paul N Moynagh, Kirby N Swatek, Paul Klenerman, Nicholas Jones, Linda V Sinclair, Donal O'Shea, Andrew E Hogan.

  Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that recognizes bacterial-derived antigens presented on MR1. Upon TCR triggering, MAIT cells respond rapidly, producing a range of effector molecules which facilitate host-protective responses in the context of microbial infections. In contrast, MAIT cell responses to viral infection are instead triggered by the recognition of cytokines, and occur independently of TCR engagement. The molecular and metabolic regulation of MAIT cell TCR responses is rapidly emerging, but there is a paucity of data on cytokine driven responses. Here, using high-resolution, quantitative proteomic analysis, we map the downstream proteome of innate cytokine (IL-18/IFNα)-activated MAIT cells, highlighting robust cytokine-driven remodeling and a signature that is distinct from the TCR-driven response. MAIT cells significantly increase protein biosynthesis in response to innate cytokine stimulation and rapidly upregulate the production of IFNγ, granzyme B, and IFN-stimulated gene 15. We demonstrate the metabolic kinetics of MAIT cell responses to cytokine stimulation and highlight a rapid but transient glycolytic burst that is uncoupled from mitochondrial remodeling and contrasts the robust metabolic profile elicited downstream of TCR engagement. Finally, we demonstrate differential contributions from both glycogen and glucose in supporting MAIT cell responses to innate cytokines and further highlight the importance of nutrient availability as a governing signal for MAIT cell fitness and effector functioning.

Keywords:  antiviral; glycogen; immunometabolism; mucosal-associated invariant T cells; type I interferon

DOI:  https://doi.org/10.1093/jimmun/vkag212
J Biol Chem. 2026 Aug 12. pii: S0021-9258(26)02300-8. [Epub ahead of print] 113428

The MHC-I related protein 1 MR1 can bind host purine catabolites.

Mohamed R Abdelaal, Xin Yi Lim, Jeffrey Y W Mak, David P Fairlie, James McCluskey, Alexandra J Corbett, Nicholas A Gherardin, Wael Awad, Jamie Rossjohn.

  The major histocompatibility complex class I-related molecule (MR1) is a non-classical antigen-presenting protein that presents a diverse array of microbial, synthetic and host-generated small metabolites to mucosal-associated invariant T (MAIT) cells and other MR1-restricted T (MR1T) cell populations. Recent studies showed that MR1 binds carbonyl-nucleobase adducts, resulting in the activation of some MR1T cell clones. However, whether endogenous canonical nucleobases and their derivatives can impact the MR1 axis remains unclear. Here, through biochemical and cellular screening of a library of canonical nucleobases and their catabolites, we demonstrate that the catabolites of purine degradation, namely uric acid, xanthine, and xanthosine, can, at high concentrations, bind MR1 and promote its intracellular retention, resulting in reduced MR1 surface expression. These purine-based nucleobases can compete with microbial and non-microbial ligands for MR1 binding. Analysis of three crystal structures of ligand-bound MR1 shows that these endogenous purine-based nucleobases adopt distinct modes of binding and interactions within the MR1 A'-pocket. Accordingly, we broaden the repertoire of MR1-ligandome by describing a group of host xanthine-based compounds that can bind MR1 and regulate its trafficking to the cell surface.

Keywords:  MR1; antigen presentation; mucosal-associated invariant T cell; nucleobases

DOI:  https://doi.org/10.1016/j.jbc.2026.113428
Chemistry. 2026 Aug 14. e71494

A Stable Isopterin Mimic of a Potent Bacterial Stimulant of T Cells.

Jeffrey Y W Mak, Huy N Hoang, Wael Awad, Xin Yi Lim, Damica D Laurie, Ryan J D Rivero, James McCluskey, Alexandra J Corbett, Jamie Rossjohn, David P Fairlie.

  Mucosal-associated invariant T cells (MAIT cells) are innate-like immune cells (T lymphocytes) that protect against bacterial infections. They are potently activated by the microbial metabolite 5-(2-oxopropylideneamino)-d-ribitylaminouracil (5-OP-RU), which bonds covalently to an amine of a specific lysine residue of the antigen-presenting protein MR1 to form an imine (Schiff base). However, 5-OP-RU undergoes rapid degradative intramolecular cyclisation in water, and more robust analogues are needed for therapeutic applications. Here, inspired by the structural similarities between 5-OP-RU and 6-formylpterin, a water-stable covalent MR1 ligand that does not activate MAIT cells, we describe the design and synthesis of a novel isopterin analogue of this microbial natural product, and show that it is both water-stable and activates reporter cells expressing the MAIT T cell receptor. Further, we present a protein-bound crystal structure and molecular dynamics simulations of this stable analogue to show that it mimics the MR1-bound conformation of 5-OP-RU. This study demonstrates the potential of this bicyclic scaffold for stabilising 5-OP-RU mimetics, advances our understanding of the molecular requirements for MR1 binding and MAIT cell activation, and informs the design and synthesis of future MAIT cell antigens as potential immunotherapeutics.

Keywords:  Schiff bases; conformation analysis; covalent ligands; immunology; natural products

DOI:  https://doi.org/10.1002/chem.71494
Int Immunopharmacol. 2026 Aug 12. pii: S1567-5769(26)01097-0. [Epub ahead of print]187 117251

Eltrombopag-associated remodeling of the MAIT, MR1+ and γδ T cells in pediatric immune thrombocytopenia.

Ekrem Ünal, Zehra Büşra Azizoğlu, Metin Çil, Ramazan Üzen, Nazly Najat Asaad, Şahin Çalik, Koray Dörteller, Enes Mehmet Türkoğlu, Yunus E Doğan, Ebru Yilmaz, Alper Özcan, Musa Karakükcü, Göksel Leblebisatan, Ahmet Eken.

  Pediatric immune thrombocytopenia (ITP) is an autoimmune cytopenia characterized by immune-mediated platelet destruction and impaired thrombopoiesis. Mucosa-associated invariant T (MAIT) cells are innate-like T cells activated by MR1-presented microbial metabolites and inflammatory cytokines, but their role in pediatric ITP and their relationship to eltrombopag therapy remain unclear. We analyzed peripheral blood mononuclear cells from healthy controls (n = 20), untreated pediatric ITP patients (n = 60), and eltrombopag-treated patients (n = 16). MAIT cells were quantified using MR1-5-OP-RU tetramers and surrogate gating (CD3+Vα7.2+CD161+). MAIT subsets, memory phenotype, chemokine receptor expression (CXCR3, CXCR5, CCR6), HLA-DR, intracellular cytokines (IFN-γ, TNF-α, IL-17 A, IL-22), and MR1+CD3- cells were analyzed by flow cytometry. Tetramer-defined MAIT cells were reduced in absolute number in pediatric ITP, including eltrombopag-treated patients, most prominently within the CD8+ subset, whereas their frequency among CD3+ T cells did not differ between untreated and eltrombopag-treated groups. In contrast, CD3+Vα7.2+CD161+ cells increased in untreated ITP and were lower in eltrombopag-treated patients. Untreated ITP patients exhibited reduced frequencies of IFN-γ- and TNF-α-producing MAIT cells, accompanied by increased IL-17-producing cells and TNF-α signal intensity. Conventional αβ T cells were reduced, whereas γδ T cells were increased; eltrombopag-treated patients exhibited γδ T-cell frequencies and cytokine-positive fractions closer to those of healthy controls. MR1+CD3- cells were expanded and displayed reduced HLA-DR expression in untreated ITP, whereas eltrombopag-treated patients showed lower MR1+CD3- frequencies and HLA-DR levels closer to healthy controls. These findings demonstrate coordinated alterations of the MAIT/MR1 axis and unconventional T-cell compartments in pediatric ITP and identify immunophenotypic differences associated with eltrombopag treatment.

Keywords:  Eltrombopag; Immune thrombocytopenia; MAIT cells; MR1; Pediatric; Γδ T cells

DOI:  https://doi.org/10.1016/j.intimp.2026.117251
Nat Rev Urol. 2026 Aug 11.

Unconventional T cells in urological cancers: catch them if you can.

Amber D Bowler, Sylvain Nguyen, Sonia Domingos-Pereira, Ilaria Lucca, Laurent Derré.

Unconventional T cells - including γδ T cells, mucosal-associated invariant T cells, natural killer T cells, double-positive (CD4⁺CD8⁺) and double-negative (CD4- CD8-) T lymphocytes - are an underexplored component of immune surveillance in urological cancers. Unlike conventional αβ T cells, these populations recognize mainly non-peptidic antigens independently of classic major histocompatibility complex restriction, enabling rapid responses to cellular stress, microbial cues and metabolic dysregulation within tissues and the tumour microenvironment. Emerging evidence suggests that each subset exhibits context-dependent behaviour across prostate cancer, bladder cancer and renal cell carcinoma, ranging from cytotoxic to immunoregulatory. Together, these unconventional T cell subsets offer a foundation for novel diagnostic and therapeutic strategies. Combination approaches currently in clinical trials that integrate checkpoint blockade, adoptive cell transfer or Bacillus Calmette-Guérin-based immunotherapy could be guided by emerging insights into how these cells recognize or are shaped by tumour cells. Research in mechanistic and translational studies involving unconventional T cells is gaining momentum and could ultimately redefine immune targeting in urological cancers.

DOI: https://doi.org/10.1038/s41585-026-01178-z
J Inflamm Res. 2026 ;19 625722

Characterization of Peripheral Blood Immune Cell Features in SSA/SSB Double‑Positive Primary Sjögren's Disease Based on Single‑Cell RNA Sequencing.

Pengrui Wang, Fei Teng, Yifei Wang, Wenqi Ji, Xinbo Yu, Guangyao Chen, Qingwen Tao.

   Objective: Primary Sjögren's disease (pSjD) is a chronic systemic autoimmune disease characterized by lymphocyte infiltration of the exocrine glands. Anti-SSA (Ro) and anti-SSB (La) antibodies are diagnostic serological markers of pSjD. However, whether the coexistence of anti-SSA and anti-SSB antibodies defines an immunologically distinct subtype at the single-cell level remains unclear.
Methods: From our established single-cell peripheral blood mononuclear cells (PBMCs) RNA sequencing database for pSjD, 3 healthy controls, 5 SSA+/SSB- pSjD patients, and 5 SSA+/SSB+ pSjD patients were selected. After quality control and removal of doublets using DoubletFinder, batch effects were corrected with Harmony. Unsupervised clustering was performed to identify major cell lineages. Subsequently, subpopulation clustering, differential gene expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, pseudotime trajectory analysis, and cell-cell communication analysis were carried out. Flow cytometry was further used to validate the findings from the single-cell sequencing.
Results: Seven major immune cell populations were identified, including T cells, B cells, monocytes/macrophages, NK cells, plasmacytoid dendritic cells (pDCs), mast cells, and platelet-megakaryocytes. Further subpopulation analysis revealed a more pronounced immune transcriptional reprogramming in the SSA+/SSB+ group compared to the SSA+/SSB- group. Specifically, cytotoxicity-related genes were upregulated in CD8+ T cells. Mucosal-associated invariant T (MAIT) cells exhibited interferon-related transcriptional program remodeling accompanied by a tissue-homing tendency. Plasma cells showed altered expression of immunoglobulin variable region genes. Monocytes/macrophages displayed changes in metabolic-related transcriptional signatures. GO/KEGG enrichment analysis, pseudotime trajectory analysis, and CellChat analysis further supported that the SSA+/SSB+ subtype possesses stronger systemic immune activation characteristics. Flow cytometry further supported altered peripheral T-cell subset distribution in SSA+/SSB+ patients, characterized by an increased proportion of CD8+ T cells and decreased proportions of CD45RA+ naïve-like T cells and MAIT cells compared with SSA+/SSB- patients.
Conclusion: SSA+/SSB+ pSjD may represent a subtype with stronger systemic immune activation, which partly explains why these patients exhibit higher disease activity in clinical practice.

Keywords:  anti-SSA antibody; anti-SSB antibody; peripheral blood mononuclear cells; primary Sjögren’s disease; single-cell RNA sequencing

DOI:  https://doi.org/10.2147/JIR.S625722
Trends Biotechnol. 2026 Aug 14. pii: S0167-7799(26)00323-9. [Epub ahead of print]

In situ programming of unconventional T cells.

Yan-Ruide Li, Haochen Nan, Youcheng Yang, Shubing Wang, Lili Yang.

  Unconventional T cells (UTCs), including γδ T cells, mucosal-associated invariant T cells, and natural killer T cells, recognize conserved nonpeptide antigens through semi-invariant T cell receptors in an human leukocyte antigen-independent manner, making them attractive candidates for broadly applicable immunotherapies. However, their clinical translation remains limited by poor spatiotemporal control of activation, functional exhaustion, and insufficient tissue homing in vivo, particularly in solid tumors. Biomaterial-based delivery systems provide a promising strategy to overcome these barriers by enabling localized and sustained delivery of UTC ligands, cytokines, and nucleic acids within diseased tissues. Through precise in situ programming of UTC responses, these platforms may enhance therapeutic efficacy and safety. This review summarizes current biomaterial-based strategies and discusses emerging opportunities for in situ UTC programming in human cancers.

Keywords:  MAIT cells; NKT cells; UTCs; biomaterial-based delivery; in situ immunoengineering; γδ T cells

DOI:  https://doi.org/10.1016/j.tibtech.2026.07.027
Arthritis Rheumatol. 2026 Aug 11.

Single-cell Profiling of Lymphoid and Myeloid Compartments Reveals Coordinated Immune Dysregulation and Enhanced Monocyte-centric Intercellular Communication in Relapsing Polychondritis.

Chenyang Lu, Yao Liang, Simin Xu, Wenyu Xu, Xinlei Jia, Weihang Zhu, Jieruo Gu, Zetao Liao, Yutong Jiang.

OBJECTIVES: Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent cartilaginous inflammation with unclear pathogenesis. The precise alterations in the peripheral immune landscape driving RP pathogenesis remain incompletely defined.
METHODS: Single-cell RNA-sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells (PBMCs) from 6 RP patients and 5 matched healthy controls (HCs). Bioinformatic analyses characterized cellular composition, transcriptomic profiles, differentially expressed genes, pathway enrichment, metabolic states, and intercellular communication. Plasma levels of alarmins and resistin were measured by ELISA.
RESULTS: RP patients exhibited a significant reduction in circulating T cells and a trend toward increased CD14+ monocytes, neutrophils, and plasma cells. Within T cells, we observed expansion of CD8+ subsets and depletion of FCER1G+ T, γδT, and mucosal-associated invariant T cells. Transcriptional programs indicative of enhanced chemotaxis, activation, differentiation, and interferon responses, alongside cytolytic ability in cytotoxic T subsets. B cells exhibited an activated phenotype, increased plasma cell differentiation potential and metabolic reprogramming. Myeloid cells display robust upregulation of alarmins (S100A8/9/12) and proinflammatory pathways. Intercellular communication analysis identified CD14+ monocytes as dominant signaling hubs, exerting extensive crosstalk via annexin, MHC, resistin, and chemokine ligand-receptor pairs, with enrichment of the ANXA1-FPR1 axis.
DISCUSSION: This study delineates a comprehensive, cell-type-revolved atlas of peripheral immune dysregulation in RP, revealing coordinated alterations in T cell activation and redistribution, B cell differentiation, myeloid-driven inflammation, and prominent alarmin-related signatures. Monocyte-centric signaling networks, potentially orchestrated through the ANXA1-FPR1 pathway, may serve as key amplifiers of systemic inflammation, and represent promising targets for therapeutic immune modulation in RP.

DOI: https://doi.org/10.1002/art.70294
Mucosal Immunol. 2026 Aug 10. pii: S1933-0219(26)00100-5. [Epub ahead of print] 100398

MAIT cells are associated with eosinophil presence and activation in the inflamed tissue of patients with eosinophilic esophagitis.

Jan Devan, Vladimir Nosi, José Pedro Loureiro, Andreas Göldi, Lucia Mori, Gennaro De Libero, Petr Hruz.

  EoE is an inflammatory condition characterised by tissue lesions and significant activation of immune cells in the oesophageal mucosa. Phenotypic and functional analyses in this study revealed widespread accumulation and activation of multiple immune cell types, with eosinophils showing the most notable expansion and activation. MAIT cells were the only activated T cell population associated with eosinophil activation, and this activation correlated with eosinophil infiltration in oesophageal tissue. Functional tests indicated that eosinophils increase MR1 expression in response to bacterial ligands and can present microbial antigens to and activate MAIT cells through an MR1- and TCR-dependent process, which, in turn, promotes cytokine release and further eosinophil activation. These findings reveal a previously unrecognised eosinophil-MAIT cell interaction that might enhance local immune responses by presenting microbial antigens that penetrate the lesioned mucosa and sustain inflammation in active EoE.

Keywords:  5-OP-Ru; Eosinophilic esophagitis; MAIT cells; MR1

DOI:  https://doi.org/10.1016/j.mucimm.2026.100398