bims-maitce 2026-07-19 papers

Issue of 2026–07–19
five papers selected by
Andy E. Hogan, Maynooth University

Sci Rep. 2026 Jul 15.

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 RORγt 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/10.1038/s41598-026-61896-7

Br J Haematol. 2026 Jul 15.

Immune features of graft-derived mucosal-associated invariant T cells predict gastrointestinal graft-versus-host disease.

Gao Mengge, Cheng Rongqi, Kong Jun, Sun Yuqian, Wang Zhidong, Sun Hui, Chang Yingjun, Huang Xiaojun, Zhao Xiaosu.

Gastrointestinal acute graft-versus-host disease (GI aGVHD) remains a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), and early risk identification and intervention are essential for improving outcomes. Mucosal-associated invariant T (MAIT) cells are mucosa-enriched unconventional T cells with major histocompatibility complex class I-related protein 1 (MR1)-restricted, major histocompatibility complex (MHC)-independent recognition, suggesting a potentially reduced risk of alloreactivity. Our previous work showed that higher graft MAIT-cell levels were associated with improved post-transplant MAIT-cell reconstitution and a lower incidence of GI aGVHD. Single-cell ribonucleic acid (RNA) sequencing (sc-RNA-seq) and murine models revealed their functional heterogeneity in immune regulation, tissue repair and chemotaxis-supporting their role as both biomarkers and therapeutic targets. In this prospective study, spectral flow cytometry was used to characterize MAIT-cell phenotypes in peripheral blood stem cell grafts. higher graft MAIT-cell abundance was associated with more robust early post-transplant MAIT-cell reconstitution and a lower risk of GI aGVHD. A three-marker predictive panel based on MAIT-cell functional markers (C-C chemokine receptor type 2 [CCR2], interleukin-4 [IL-4], interleukin-17A [IL-17A]) achieved an area under the receiver operating characteristic curve (AUC) of 0.80, increasing to 0.85 after adjustment for clinical covariates. These findings identify graft-derived MAIT cells as a predictive immune-associated biomarker for GI aGVHD, enabling pre-transplant risk stratification and supporting precision prevention strategies. Trial registration: ChiCTR2500095349.

Keywords: allogeneic haematopoietic stem cell transplantation; gastrointestinal acute graft‐versus‐host disease; mucosal‐associated invariant T cells; risk score

DOI: https://doi.org/10.1111/bjh.70683

Patterns (N Y). 2026 Jul 10. 7(7): 101562

SHIELD: A weakly supervised graph attention neural network for decoding disease-relevant cell-cell interactions.

Vivek Sehra, Benjamin Ruf, Gabriel Duval, Sepideh Babaei, Manfred Claassen.

Multiplexed tissue imaging enables detailed study of cell-cell interactions in disease, yet systematic, interpretable, and supervised computational methods for inferring such interactions remain scarce. We present SHIELD (spatially enhanced immune landscape decoding), a graph attention network framework that quantifies disease-relevant cell-cell interactions through learned attention scores, without relying on prior biological assumptions such as ligand-receptor databases. Validated across three multiplexed tissue imaging datasets-hepatocellular carcinoma (HCC), colorectal cancer (CRC), and type 1 diabetes (T1D)-SHIELD identifies rare mucosal-associated invariant T (MAIT) cell-macrophage interactions in HCC, suppressive CD8+ T cell-macrophage interactions enriched in CRC non-responders, and β cell interactions with cytotoxic and helper T cells across T1D disease stages. In all contexts, SHIELD reconstructs known and biologically meaningful interactions, offering a robust, interpretable tool for spatial tissue analysis and data-driven mechanistic discovery.

Keywords: cancer; diabetes; graph attention network; highly multiplexed tissue imaging; single-cell biology; spatial biology

DOI: https://doi.org/10.1016/j.patter.2026.101562

Res Sq. 2026 Jul 10. pii: rs.3.rs-10046801. [Epub ahead of print]

Multi-hit genetic lesions and a stress-imprinted immune transcriptome define the inflammatory pathology in ALS patients.

Ao Mei, Dipanarine Jewett, Anahid Jewett, Kawaljit Kaur, Subramaniam Malarkannan.

Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease whose peripheral immune architecture remains incompletely defined. Here, we integrated whole-genome sequencing and single-cell RNA sequencing to define genomic and immune correlates of ALS. Genome-wide analysis of a monozygotic twin pair discordant for ALS pathology identified shared ALS-associated variants, as well as patient-enriched variants in genes linked to RNA metabolism, neurodegeneration, and immune inflammation, supporting a multilayered genetic architecture. Single-cell profiling of 40,484 peripheral blood mononuclear cells from three ALS patients and two healthy individuals, including 33,667 cells retained after quality control, resolved 13 immune clusters and revealed broad remodeling of the peripheral immune compartment, with relative enrichment of natural killer, mucosal-associated invariant T, and γδ T-cell populations. Across immune subsets, ALS samples exhibited inflammatory and stress-adapted transcriptomic programs, including TNF-α/NF-κB, IFN-γ, hypoxia, and ribosomal stress pathways. These data support a model in which multi-hit genetic susceptibility converges on a stress-induced immune transcriptome, marked uniquely by innate lymphocyte activation in ALS patients.

DOI: https://doi.org/10.21203/rs.3.rs-10046801/v1

STAR Protoc. 2026 Jul 15. pii: S2666-1667(26)00360-6. [Epub ahead of print]7(3): 104707

Protocol for deep phenotyping of human antigen-specific T cells across conventional and unconventional subsets by 22-color spectral flow cytometry.

Jiahui Du, Mingzhe Zeng, Ziqian He, Xiang Li, Shuxun Liu, Zhiqing Li.

Analyzing antigen-specific T cells at the subset level is crucial for studying antiviral immunity and vaccine efficacy. We present a 22-color spectral flow cytometry protocol to characterize these cells from human PBMCs, covering conventional αβT and unconventional (MAIT, γδ T) subsets. We describe steps for PBMC thawing and plate setup, peptide stimulation, three-step surface staining, and intracellular staining. We then detail procedures for sample acquisition and Flowjo data analysis. This approach enables precise immunophenotyping with limited samples.

Keywords: Cell culture; Flow Cytometry; Immunology

DOI: https://doi.org/10.1016/j.xpro.2026.104707