bims-maitce Biomed News
on MAIT cells
Issue of 2025–04–06
six papers selected by
Andy E. Hogan, Maynooth University
  1. Human Neonatal MR1T Cells Have Diverse TCR Usage, are Less Cytotoxic and are Unable to Respond to Many Common Childhood Pathogens.
  2. Circulating Mucosal-associated Invariant T Cells Predict Early Neurological Deterioration in Acute Ischemic Stroke.
  3. Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway.
  4. The clinical landscape of CAR-engineered unconventional T cells.
  5. Restoration of IFN-γ-Producing MAIT Cell Correlates to Beneficial Allergen Immunotherapy in Allergic Rhinitis Patients.
  6. Single-cell map of innate-like lymphocyte response to Francisella tularensis infection reveals interleukin-17-dependent protection by MAIT cells.
  1. bioRxiv. 2025 Mar 18. pii: 2025.03.17.643805. [Epub ahead of print]
    Human Neonatal MR1T Cells Have Diverse TCR Usage, are Less Cytotoxic and are Unable to Respond to Many Common Childhood Pathogens.
    Dylan Kain, Wael Awad, G W McElfresh, Meghan Cansler, Gwendolyn M Swarbrick, Kean Chan Yew Poa, Conor McNeice, Gregory Boggy, Katherine Rott, Megan D Null, David M Lewinsohn, Jamie Rossjohn, Benjamin N Bimber, Deborah A Lewinsohn.
      Neonatal sepsis is a leading cause of childhood mortality. Understanding immune cell development can inform strategies to combat this. MR1-restricted T (MR1T) cells can be defined by their recognition of small molecules derived from microbes, self, and drug and drug-like molecules, presented by the MHC class 1-related molecule (MR1). In healthy adults, the majority of MR1T cells express an invariant α-chain; TRAV1-2/TRAJ33/12/20 and are referred to as mucosal-associated invariant T (MAIT) cells. Neonatal MR1T cells isolated from cord blood (CB) demonstrate more diversity in MR1T TCR usage, with the majority of MR1-5-OP-RU-tetramer(+) cells being TRAV1-2(-). To better understand this diversity, we performed single-cell-RNA-seq/TCR-seq (scRNA-seq/scTCR-seq) on MR1-5-OP-RU-tetramer(+) cells from CB (n=5) and adult participants (n=5). CB-derived MR1T cells demonstrate a less cytotoxic/pro-inflammatory phenotype, and a more diverse TCR repertoire. A panel of CB and adult MAIT and TRAV1-2(-) MR1T cell clones were generated, and CB-derived clones were unable to recognize several common riboflavin-producing childhood pathogens ( S. aureus, S. pneumoniae, M. tuberculosis ). Biochemical and structural investigation of one CB MAIT TCR (CB964 A2; TRAV1-2/TRBV6-2) showed a reduction in binding affinity toward the canonical MR1-antigen, 5-OP-RU, compared to adult MAIT TCRs that correlated with differences in β-chain contribution in the TCR-MR1 interface. Overall, this data shows that CB MAIT and TRAV1-2(-) MR1T cells, express a diverse TCR repertoire, a more restricted childhood pathogen recognition profile and diminished cytotoxic and pro-inflammatory capacity. Understanding this diversity, along with the functional ability of TRAV1-2(-) MR1T cells, could provide insight into increased neonatal susceptibility to infections.
    DOI:  https://doi.org/10.1101/2025.03.17.643805
  2. J Stroke Cerebrovasc Dis. 2025 Mar 27. pii: S1052-3057(25)00080-1. [Epub ahead of print] 108301
    Circulating Mucosal-associated Invariant T Cells Predict Early Neurological Deterioration in Acute Ischemic Stroke.
    Ruihua Liu, Lulu Pei, Jiacheng Liu, Liang Peng, Cairu Guo, Yan Li, Zhihui Duan, Yanjiao Du, Dandan Shang, Shao Li, Yunting Zhang, Bo Song.
       BACKGROUND: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that rapidly produce cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17) upon activation. The immune response is crucial in stroke-related injury. However, few studies have investigated the role of MAIT cells in ischemic brain injury. This study assessed the predictive value of circulating MAIT cells in acute ischemic stroke (AIS) and early neurological deterioration (END).
    METHODS: We prospectively and continuously enrolled AIS patients within 72 h of stroke onset and included controls. END was defined as a ≥2-point increase in the National Institutes of Health Stroke Scale score within the first 72 h. Receiver operating characteristic curves were used to evaluate the predictive value of MAIT cells for END.
    RESULTS: This study included 188 AIS patients and 135 controls, with 50 (26.6%) AIS patients experiencing END. After adjusting for all potential confounders, circulating MAIT cell frequencies were lower in AIS patients than in controls (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.70-0.97, P = 0.02). IL-17 and TNF-α levels were significantly higher in AIS patients and negatively correlated with MAIT cell frequencies (R = -0.26, P < 0.05; R = -0.19, P < 0.05). Multivariate logistic regression analysis revealed that MAIT cell frequencies were lower in patients with END compared to those without END (OR: 0.74, 95% CI: 0.55-0.96, P = 0.03). The area under the curve for MAIT cells in END prediction was 0.641 (95% CI: 0.548-0.725, P < 0.05).
    CONCLUSIONS: MAIT cell frequency was reduced in AIS patients and may serve as a predictive marker for END. Modulating these cells could be a novel AIS treatment strategy.
    Keywords:  Acute ischemic stroke; Early neurological deterioration; Interleukin-17; Mucosal-associated invariant T cells; neuroinflammation
    DOI:  https://doi.org/10.1016/j.jstrokecerebrovasdis.2025.108301
  3. Commun Biol. 2025 Apr 01. 8(1): 538
    Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway.
    Yusi Zhang, He Liu, Dalu Liu, Huiyuan Zhang, Ying Ma, Na Li, Chunmei Zhang, Manling Xue, Fenglan Wang, Xiaozhou Jia, Hui Zhang, Kang Tang, Xiaoyue Xu, Shijia Wang, Yiwen Wei, Xiaojing Yang, Jiajia Zuo, Lihua Chen, Boquan Jin, Yun Zhang.
      Hantaan virus (HTNV) triggers an epidemic of hemorrhagic fever with renal syndrome (HFRS), which is predominantly prevalent in Asia. Mucosal-associated invariant T (MAIT) cells, categorized as innate-like T lymphocytes, perform crucial functions in the innate host defense mechanism during virus infection. We previously showed that MAIT cells played antiviral roles in vitro. But marked reduction of MAIT cells was present in the peripheral blood of HFRS patients. Till now, the role of MAIT cells in vivo and the mechanisms of HTNV-induced the MAIT cell deficiency have not yet been fully explored. In this study, by combining the clinical samples, MAIT deficiency mice and in vitro infected MAIT cell models, we find that pyroptosis was the main reason of MAIT cell loss in the peripheral blood of HFRS patients. The molecular mechanisms are related to the overload of calcium in the endoplasmic reticulum (ER) of MAIT cells, which subsequently induces inosital-requiring enzyme-1α (IRE1α)-mediated ER-stress and following pyroptosis. ER-stress inhibitor can reverse the pyroptosis of MAIT cells during HTNV infection. In conclusion, this study firstly reveals the underlying molecular mechanisms for the deficiency of MAIT cells during HTNV infection, and suggests a potential way to stabilize the MAIT cells population in HFRS.
    DOI:  https://doi.org/10.1038/s42003-025-07979-z
  4. Trends Cancer. 2025 Mar 27. pii: S2405-8033(25)00069-X. [Epub ahead of print]
    The clinical landscape of CAR-engineered unconventional T cells.
    Yan-Ruide Li, Yichen Zhu, Yuning Chen, Lili Yang.
      Unconventional T cells, such as invariant natural killer T (iNKT), γδ T, and mucosal-associated invariant T (MAIT) cells, play a pivotal role in bridging innate and adaptive immunity. Their capacity for rapid tumor targeting and effective modulation of the tumor microenvironment (TME) makes them promising candidates for cancer immunotherapy. Advances in chimeric antigen receptor (CAR) engineering have further highlighted their therapeutic potential, particularly for treating challenging cancers. Notably, these cells exhibit favorable safety profiles, enhancing their viability as off-the-shelf therapeutic options. We provide a comprehensive analysis of the clinical applications of CAR-engineered unconventional T cells, focusing on genetic modifications, manufacturing processes, preconditioning regimens, and dosing strategies. We discuss successful examples from recent clinical trials and explore future directions for utilizing these cells in cancer therapy and beyond.
    Keywords:  cancer immunotherapy; chimeric antigen receptor engineering; invariant natural killer T cell; mucosal-associated invariant T cell; unconventional T cell; γδ T cell
    DOI:  https://doi.org/10.1016/j.trecan.2025.03.001
  5. Clin Exp Allergy. 2025 Apr 02.
    Restoration of IFN-γ-Producing MAIT Cell Correlates to Beneficial Allergen Immunotherapy in Allergic Rhinitis Patients.
    Ying Jiang, Xin Wang, Qing Jiang, Hao Chen, Lin Yang, Wei Wang, Junmei Weng, Mi Wu, Ting Zhou, Yin Yao, Shuyan Guo, Jin Xiong, Xiang Lu, Rongfei Zhu, Xiufang Weng.
       BACKGROUND: Mucosal-associated invariant T cells (MAIT) are emerging as important regulators at mucosal surfaces. While these cells have been linked to a Th1-biased immune response and support for B cells, their roles in allergic diseases characterised by type 2 inflammation remain elusive. The study seeks to characterise MAIT cells in house dust mite (HDM)-induced allergic rhinitis (AR) and subsequent allergen immunotherapy (AIT), aiming to elucidate their clinical significance in AR and potential to enhance AIT effectiveness.
    METHODS: MAIT cells were assessed in patients with AR and individuals undergoing AIT. The ratio and cytokine-producing capacity of these cells were analysed to explore their correlations with AR progression and their responsiveness to HDM extracts and MAIT cell-specific agonists.
    RESULTS: In AR patients, there was an increase in the ratios of circulating MAIT cells and tonsil follicular T helper-like MAIT cells, alongside a decrease in the IFN-γ-producing MAIT cells. AIT restored their IFN-γ producing capacity, which was further boosted by T cell receptor (TCR) activation using MAIT cell-specific agonist-loaded artificial antigen-presenting cells (aAPCs). Synergistic effects of aAPCs and HDM enhance MAIT cell activation and IFN-γ production while reducing HDM-induced IgE levels in PBMC cocultures. Moreover, higher ratios of MAIT cells and IFN-γ-producing MAIT cells correlated with decreased IgE and increased IgG4 and improved clinical outcomes during AIT.
    CONCLUSIONS: These findings underscore the compromised IFN-γ-producing MAIT cells in AR and their restoration following AIT and TCR stimulation, highlighting the cell's therapeutic potential and predictive value for clinical outcomes in AR and AIT.
    Keywords:  B‐lymphocyte cell; allergen immunotherapy; allergic rhinitis; house dust mite; mucosal‐associated invariant T cells
    DOI:  https://doi.org/10.1111/cea.70051
  6. iScience. 2025 Mar 21. 28(3): 111810
    Single-cell map of innate-like lymphocyte response to Francisella tularensis infection reveals interleukin-17-dependent protection by MAIT cells.
    G Donald Okoye, Amrendra Kumar, Farshad Ghanbari, Nowrin U Chowdhury, Lan Wu, Dawn C Newcomb, Luc Van Kaer, Holly M Scott Algood, Sebastian Joyce.
      Early immune dynamics during the initiation of fatal tularemia caused by Francisella tularensis infection remain unknown. Unto that end, we generated a transcriptomic map at single-cell resolution of the innate-like lymphocyte responses to F. tularensis live vaccine strain (LVS) infection of mice. We found that both interferon-γ (IFN-γ)-producing type 1 and interleukin-17 (IL-17)-producing type 3 innate-like lymphocytes expanded in the infected lungs. Natural killer (NK) and NKT cells drove the type 1 response, whereas mucosal-associated invariant T (MAIT) and γδ T cells drove the type 3 response. Furthermore, tularemia-like disease resistant NKT cell-deficient, Cd1d -/- mice accumulated more MAIT1 cells, MAIT17 cells, and cells with a hybrid phenotype between MAIT1 and MAIT17 cells than wild-type mice. Critically, adoptive transfer of LVS-activated MAIT cells from Cd1d -/- mice, which were enriched in MAIT17 cells, was sufficient to protect LVS-susceptible, immunodeficient RAG2 -/- mice from severe LVS infection-inflicted pathology. Collectively, our findings position MAIT cells as potential mediators of IL-17-dependent protection from pulmonary tularemia-like disease.
    Keywords:  Cell biology; Immunology; Microbiology
    DOI:  https://doi.org/10.1016/j.isci.2025.111810
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