bims-maitce Biomed News
on MAIT cells
Issue of 2026–02–15
eight papers selected by
Andy E. Hogan, Maynooth University
  1. Antigenic stimulation in conjunction with cytokine is required for mediating IL-17A production in human MAIT cells.
  2. MR1-Mediated Activation of Mucosal-Associated Invariant T Cells by Oral Lichen Planus-Associated Fibroblasts.
  3. Elucidating Ligand Charge Effects in MR1 Cell-Surface Translocation Using Molecular Simulations.
  4. Immunophenotyping of Mouse Colonic Unconventional T Cells by Mapping Cell Phenomics With 22-Color Flow Cytometry Assays.
  5. Unexplored Domain: The Unconventional T Cells in the Male Genitourinary Tract and Related Diseases.
  6. Immune triad microenvironments define coordinated activation architecture in psoriatic disease.
  7. Shared T-Cell Receptor Repertoire in the Tonsils of Patients with Immunoglobulin A Nephropathy.
  8. Editorial: Community series in the role of CD1- and MR1-restricted T cells in immunity and disease: volume III.
  1. bioRxiv. 2026 Jan 30. pii: 2026.01.27.702041. [Epub ahead of print]
    Antigenic stimulation in conjunction with cytokine is required for mediating IL-17A production in human MAIT cells.
    Se-Jin Kim, Dylan Kain, Deborah A Lewinsohn, Gwendolyn M Swarbrick, Meghan E Cansler, Benjamin N Bimber, G W McElfresh, Emily B Wong, Sharon Khuzwayo, Thomas Riffelmacher, David M Lewinsohn.
      Mucosal-associated invariant T (MAIT) cells are donor unrestricted T cells capable of both antigen-specific adaptive responses and cytokine driven innate-like functions. Although human MAIT cells uniformly express ROR γ t and IL23R , they generally produce IFN-γ, and only a small fraction produces IL-17. Recent studies show that combined TCR and cytokine stimulation can elicit functional heterogeneity in blood-derived MAIT cells. Here, we investigate the role of IL-23/IL-23R signaling in mediating the function and transcriptional profiles of lung MAIT cell clones. We demonstrate that BAL-derived lung MAIT cell clones exhibit distinct cytokine profiles and variable IL23R expression. Short-term IL-23 stimulation triggers clone-specific transcriptional programs and IL23R -dependent upregulation of type 17-associated genes. Prolonged conditioning of lung MAIT cell clones with TCR (5-OP-RU) and cytokine (IL-23) stimulation induces stable IL-17A production along with unique transcriptional changes. TCR + IL-23 conditioning alone upregulates clone-specific and shared cytoskeletal/structural gene programs, whereas subsequent PMA/Ionomycin stimulation further induces IL-12 family signaling and metabolic genes. Together, these findings demonstrate that IL23R expression and TCR signaling are required for IL-17A production, highlighting that these conditions may be met in tissue environments where MR1-specific antigens and proinflammatory cytokines coexist.
    DOI:  https://doi.org/10.64898/2026.01.27.702041
  2. Oral Dis. 2026 Feb 12.
    MR1-Mediated Activation of Mucosal-Associated Invariant T Cells by Oral Lichen Planus-Associated Fibroblasts.
    Xiaoli Wu, Qian Mi, Yuhe Chen, Xiaoheng Xu, Xiaoqin Xiong, Wenxia Meng.
       BACKGROUND: Oral lichen planus (OLP) is a chronic immune-mediated inflammatory disease with malignant potential, and its local inflammatory microenvironment is closely related to mucosal-associated invariant T cells (MAIT). Our prior work established OLP-associated fibroblasts (OLP/AFs) in creating the inflammatory milieu, but their interaction with MAIT cells remains unexplored. This study aims to investigate how OLP/AFs interact with MAIT cells.
    MATERIALS AND METHODS: Oral mucosal samples from OLP patients and healthy controls were selected for flow cytometry to detect MAIT cells. MR1 expression on fibroblasts was quantified via RT-qPCR, Western blot, immunohistochemistry, and immunofluorescence. For functional assays, OLP/AFs were stimulated with formaldehyde-fixed Escherichia coli (E. coli) to induce MR1 surface expression, then co-cultured with PBMCs±anti-MR1 blocking antibody and evaluated the activation status of MAIT.
    RESULTS: MR1 expression and MR1+ fibroblast density were significantly elevated in OLP lesions compared to healthy controls. OLP/AFs demonstrated higher baseline MR1 expression than normal fibroblasts, which was further enhanced following E. coli stimulation. Co-culture of E. coli-stimulated OLP/AFs with peripheral blood mononuclear cells induced marked activation of MAIT cells. This was evidenced by significantly increased frequencies of CD69+ MAIT cells and elevated secretion of pro-inflammatory cytokines and cytotoxic molecules.
    CONCLUSION: OLP/AFs activate MAIT cells via an MR1-dependent mechanism.
    Keywords:  fibroblast; major histocompatibility complex class I–related protein; mucosal‐associated invariant T cell; oral lichen planus
    DOI:  https://doi.org/10.1111/odi.70238
  3. J Chem Inf Model. 2026 Feb 10.
    Elucidating Ligand Charge Effects in MR1 Cell-Surface Translocation Using Molecular Simulations.
    Toshiki Fujii, Mitsugu Araki, Shigeyuki Matsumoto, Biao Ma, Takao Otsuka, Gert-Jan Bekker, Narutoshi Kamiya, Hiroaki Ohno, Shinsuke Inuki, Yasushi Okuno.
      The major histocompatibility complex class I-related protein 1 (MR1) is an antigen-presenting protein that binds its ligand in the endoplasmic reticulum and presents the resulting complex on the cell surface to regulate mucosal-associated invariant T (MAIT) cell function. The MAIT cells play an important role in infection defense and tissue repair and are involved in various pathological conditions. Therefore, MR1 and its ligands, which act as MAIT cell activation triggers, have garnered increasing attention. Notably, MR1 levels on the cell surface vary greatly depending on its ligands. However, the ligand recognition mechanism of MR1, as well as the structure-activity relationship of its ligands, remains poorly understood. In this study, we conducted computational analyses on the interactions between MR1 and its ligands and determined the stability of the MR1-ligand complex structures to clarify the chemical properties of ligands involved in the regulation of MR1 levels on the cell surface. Our findings provide evidence that covalent and noncovalent ligands bind to MR1 in an anionic state rather than in a previously assumed neutral state, thereby stabilizing the resulting MR1-ligand complex. Furthermore, neutralization of the positive charge derived from Arg9 upon binding of anionic ligands was identified as a key factor that contributes to the enhancement of its levels on the cell surface. Our results lay a strong foundation for further studies delving into the molecular mechanisms of ligand recognition and cell-surface localization of MR1 and will facilitate the design of ligands that activate MAIT cells.
    DOI:  https://doi.org/10.1021/acs.jcim.5c02141
  4. Phenomics. 2025 Oct;5(5): 551-564
    Immunophenotyping of Mouse Colonic Unconventional T Cells by Mapping Cell Phenomics With 22-Color Flow Cytometry Assays.
    Lehan Pan, Chunting Shen, Shiyang Huang, Yingchi Yang, Zhongtao Zhang, Dan Tian.
      The intestinal epithelium is continually exposed to food-derived antigens and microbiota. This continual exposure requires a delicate immune homeostasis for food tolerance and protection against infection. Unconventional T lymphocytes, including γδT cells, Natural killer T (NKT) cells, Mucosal-Associated Invariant T (MAIT) cells, and Double-Negative T (DNT) cells, typically reside in the mucosal tissue, such as the colon. These cells play crucial roles in maintaining the integrity of the mucosal barrier and immune homeostasis through cytokine secretion and direct cell-mediated effects. Understanding the proportions and functional status of unconventional T lymphocytes in the colon is crucial for elucidating disease mechanisms. In this study, we developed a 22-color flow cytometry panel for comprehensive immunophenotyping of unconventional T lymphocytes in the murine colon. Our optimized protocol included antibody titration and customized gating strategies. We identified distinct populations of unconventional T lymphocytes, including γδT cells, NKT cells and DNT cells, and compared them with conventional T lymphocyte subsets (CD4+ T, CD8αα+ T, and CD8αβ+ T). We assessed their proliferation, cytotoxicity, cytokine production, and immune checkpoint molecule expression. Inhibitory receptor levels on intraepithelial and lamina propria unconventional T lymphocytes differed, suggesting distinct local environments and regulatory mechanisms. Our findings elucidate the status and function characteristics of unconventional T cells in colonic tissues, providing insights for mechanistic studies and the development of therapies for gastrointestinal diseases.
    Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-025-00237-6.
    Keywords:  Activation markers; Cytokines; Immune checkpoint molecules; Immunophenotyping; Intestinal lymphocyte; Multi-parametric flow cytometry
    DOI:  https://doi.org/10.1007/s43657-025-00237-6
  5. FASEB J. 2026 Feb 28. 40(4): e71566
    Unexplored Domain: The Unconventional T Cells in the Male Genitourinary Tract and Related Diseases.
    Qingyuan Cheng, Yuxi Liu, Ruiting Wu, Jiaxun Wang, Liman Li, Bin Zhou, Fuping Li.
      The male genitourinary tract develops a sophisticated immune microenvironment within individual organs and across different organs to maintain tolerance toward germ cells and defense against invasive pathogens, a network orchestrated by diverse immune cells including a special T cell subset termed unconventional T cells. Unconventional T cells, mainly encompassing γδ T cells, natural killer T (NKT) cells, and mucosal-associated invariant T (MAIT) cells, exhibit non-classical antigen recognition, integrate features of innate and adaptive immunity, and manifest tissue-specific functional specialization. Despite their crucial roles in local mucosal immunity and inflammatory regulation, the systematic characterization of these unique T cell subgroups within the male genitourinary system remains largely underexplored. To this end, our comprehensive review systematically summarized knowledge regarding the subsets, distribution, and functions of unconventional T cell populations across the anatomical regions of the male genitourinary tract-findings derived from multimodal methodologies such as immunohistochemical analyses, multicolor flow cytometry, and the latest insights from single-cell transcriptomic sequencing. Moreover, we elucidated the disparities of unconventional T cells in peripheral blood, urine and semen under physiological and pathological conditions, and discussed their clinical significance as promising biomarkers and therapeutic potential in diseases such as male genitourinary tract infection and immune-related infertility.
    Keywords:  MAIT cells; NKT cells; human semen; male genitourinary tract; γδ T cells
    DOI:  https://doi.org/10.1096/fj.202502564R
  6. Int Immunopharmacol. 2026 Feb 08. pii: S1567-5769(26)00181-5. [Epub ahead of print]173 116337
    Immune triad microenvironments define coordinated activation architecture in psoriatic disease.
    Caio Santos Bonilha.
      Psoriatic inflammation reflects contributions from several leukocyte lineages, yet organisational patterns of immune cell cooperation remain largely unexplored. Immune triads, defined as combinations of three lineages within a common spatial microenvironment, represent spatial patterns that may shed light on the inflammatory organisation of psoriasis. Triads formed by dendritic cells (DC), T cells (T) and natural killer cells (NK) integrate antigen presentation and cytotoxic pathways relevant to psoriatic inflammation. Triads that incorporate monocytes, neutrophils and innate-like T cells capture divergent recognition pathways, with γδ T cells providing rapid stress surveillance and mucosal-associated invariant T cells (MAIT) exerting cytokine-driven effector responses. Together these lineage features suggest that these triads may act as immunological contexts that potentially contribute to the architecture of psoriatic inflammation, supporting a systematic assessment of their spatial positioning and activation profiles. This work integrates peripheral CITE-seq profiling with spatial transcriptomics from psoriatic disease to measure systemic activation synchrony, identify triad niches across tissue layers and characterise activation patterns within their spatial microenvironments. The analysis reveals a marked systemic activation synchrony within DC-T-NK triads together with a consistent enrichment of all three triads in psoriatic lesions and a dominant localisation of triad co-occupation within epidermal regions. Within the epidermis, coordinated activation is evident in both DC-T-NK and monocyte-MAIT-neutrophil triads, while severity-linked signals are most prominent in MAIT-containing triads. These findings demonstrate that immune triads provide a unifying framework that connects coordinated activation in tissue with clinically meaningful features of psoriatic inflammation.
    Keywords:  Dendritic cell; MAIT cell; NK cell; Spatial transcriptomics; T cell; Γδ T cell
    DOI:  https://doi.org/10.1016/j.intimp.2026.116337
  7. Kidney360. 2026 Feb 10.
    Shared T-Cell Receptor Repertoire in the Tonsils of Patients with Immunoglobulin A Nephropathy.
    Kazunori Satokata, Shin Goto, Hiroki Yamaguchi, Hirofumi Watanabe, Nao Takahashi, Koichi Higashi, Suguru Yamamoto, Yoshikatsu Kaneko, Arata Horii, Ken Kurokawa, Ichiei Narita.
       BACKGROUND: Aberrant mucosal immune responses are underlying causes of Immunoglobulin A nephropathy (IgAN), the most prevalent type of chronic glomerulonephritis. However, the role of T cells in IgAN pathogenesis remains elusive. To address this knowledge gap, we profiled the T-cell receptor (TCR) repertoire in the tonsils of patients with IgAN.
    METHODS: This study included 27 and 20 patients with biopsy-confirmed IgAN and recurrent tonsillitis (RT), respectively, who underwent tonsillectomy. The TCR repertoire was determined by high-throughput sequencing coupled with unbiased adaptor ligation polymerase chain reaction (PCR). Furthermore, the usage of variable and joining regions in TCRα (TRA) and β (TRB) genes in each group was assessed. TRA clonotypes shared among the patients were characterized by complementary determining region 3 (CDR3) lengths, types of mucosal-associated invariant T (MAIT) cells, hydrophobicity, and their relationships with tonsillar galactose-deficient IgA1 (Gd-IgA1) and tonsillar IgA-binding indices of tonsillar bacteria.
    RESULTS: The TRA repertoire exhibited significantly lower similarity in patients with IgAN than did in RT cases (P < 0.001). Sharing TRA clonotypes among patients with IgAN was significantly sparser than that among RT cases. The relative abundance of shared TRA clonotypes with shorter CDR3 lengths was significantly increased in patients with IgAN (P_adj = 0.041), which was characterized by low MAIT match scores. Significant negative correlations were observed between the MAIT scores and hydrophobicity for these TRA clonotypes in patients with IgAN. The relative abundances of these clonotypes significantly and positively correlated with the IgA binding indices of the phylum Bacteroidetes (P_adj = 0.008) in both groups and tonsillar Gd-IgA1 levels in patients with IgAN (P = 0.035).
    CONCLUSIONS: The results in this study suggest aberrant T-cell subsets involvement in tonsillar immunity in patients with IgAN.
    DOI:  https://doi.org/10.34067/KID.0000001154
  8. Front Immunol. 2026 ;17 1783936
    Editorial: Community series in the role of CD1- and MR1-restricted T cells in immunity and disease: volume III.
    Kazuya Iwabuchi, Luc Van Kaer.
      
    Keywords:  CD1; MR1; immune-mediated disease; immunity; mucosal-associated invariant T cells; natural killer T cells; non-peptide antigens; unconventional T cells
    DOI:  https://doi.org/10.3389/fimmu.2026.1783936
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