bims-maitce 2026-08-09 papers

Issue of 2026–08–09
four papers selected by
Andy E. Hogan, Maynooth University

iScience. 2026 Aug 21. 29(8): 116957

Isabelle Nel, Gaëlle Vermillac, Léo Bertrand, Lucie Beaudoin, Etienne Larger, Ioannis Theodorou, Agnès Lehuen.

Type 1 diabetes (T1D) is an autoimmune disease for which mouse models have highlighted a role for innate-like T cells, although evidence in humans remains limited. Here, we integrated for the first time flow cytometry analyses of invariant natural killer T (iNKT), γδT, and mucosal-associated invariant T (MAIT) cells from the same adults with recent-onset T1D (n = 21), long-term T1D (n = 47), and healthy controls (n = 55). Recent-onset T1D was associated with reduced frequencies of TNFα-producing iNKT and γδT cells, whereas long-term T1D showed more pronounced alterations, including increased PD-1 expression and an exhaustion-like phenotype across all three populations. Principal-component analysis integrating iNKT, γδT, and MAIT cell parameters positioned recent-onset patients between healthy controls and long-term T1D patients. Exploratory predictive modeling suggests that MAIT cell markers may contribute to disease classification. Together, these findings provide an integrated view of innate-like T cell alterations in adult T1D and highlight their relationship with disease duration.

Keywords: MAIT cells; autoimmunity; human; iNKT cells; innate-like T cells; type 1 diabetes; γδT cells

DOI: https://doi.org/10.1016/j.isci.2026.116957

Front Immunol. 2026 ;17 1886594

"From inflammation to fibrosis: a proposed role of mucosal-associated invariant T cells in lichen sclerosus - a conceptual framework".

Marta Kasprowicz-Furmańczyk, Agnieszka Owczarczyk-Saczonek.

Lichen sclerosus (LS) is a chronic inflammatory and fibrosing dermatosis with a well-documented autoimmune background and a dominant Th1/Th17-driven immune response. Despite growing insight into its immunopathogenesis, the mechanisms linking persistent inflammation to progressive fibrosis remain unclear. Mucosal-associated invariant T cells (MAIT cells) are innate-like lymphocytes enriched in epithelial tissues, characterized by rapid activation and robust production of proinflammatory cytokines. Although alterations in MAIT cells frequency and function have been described in autoimmune and fibrotic disorders, their role in LS has not yet been elucidated. This review integrates current knowledge on MAIT cells biology and proposes a conceptual framework for their potential involvement in LS, largely based on extrapolation from studies in other inflammatory and fibrotic conditions. We hypothesize that MAIT cells may contribute to disease progression by amplifying Th1/Th17 responses, promoting epithelial damage and indirectly supporting fibroblast activation through cytokine-mediated pathways, including the TGF-β axis. Furthermore, their responsiveness to microbial-derived ligands and inflammatory cytokines suggests a role in sustaining chronic immune activation within a dysregulated tissue microenvironment. Under chronic inflammatory conditions, MAIT cells may shift toward a proinflammatory and profibrotic phenotype, thereby contributing to the transition from inflammation to fibrosis. This hypothesis-generating framework requires experimental validation but may provide new insights into LS pathogenesis and potential therapeutic targets.

Keywords: MAIT cells; fibrosing disease; inflammatory disease; lichen sclerosus; mucosal-associated invariant T cells

DOI: https://doi.org/10.3389/fimmu.2026.1886594

Front Immunol. 2026 ;17 1859932

CCL20-CCR6 axis mediates mucosal-associated invariant T-M2 macrophage crosstalk to drive immune dysregulation in liver cirrhosis.

Bochen Chen, Ruoling Li, Shuya Zhang, Yiting Lou, Shuo Zhang, Jiaheng Lou, Jingcheng Zhang, Chuyun Xu, Tao Jiang, Yuanlin Lv.

Introduction: Cirrhosis is the end-stage of chronic liver disease characterized by progressive hepatic fibrosis and persistent immune dysregulation, yet the mechanisms by which immune cell crosstalk drives disease progression remain poorly understood.
Methods: In the present study, we integrated bulk and single-cell transcriptomic analyses with immunofluorescence validation to investigate the role of the CCL20-CCR6 axis in MAIT cells-macrophages interactions during cirrhosis progression.
Results: We identified eight core cirrhosis-associated immune genes (OGN, IL32, CCL19, PDGFA, CCL20, NTS, SEMA3C, HSPA2), among which CCL20 was selectively enriched in mucosal-associated invariant T cells (MAIT) and closely associated with their activation- and exhaustion-related transcriptional profiles. Cell-cell communication analysis revealed that the CCL20-CCR6 axis may specifically mediate bidirectional interactions between MAIT cells and M2 macrophages, forming a disease-specific positive feedback loop within the cirrhotic microenvironment. Immunofluorescence staining further confirmed the enrichment and colocalization of CCL20, MAIT cells, and M2 macrophages in cirrhotic tissues.
Discussion: Collectively, these findings support the CCL20-CCR6 axis as a key regulator of hepatic immune dysregulation and fibrotic progression in liver cirrhosis, highlighting its potential as both a biomarker of disease activity and a therapeutic target for cirrhosis intervention.

Keywords: CCL20; M2 macrophages; MAIT cells; cirrhosis; immune dysregulation; single-cell transcriptomics

DOI: https://doi.org/10.3389/fimmu.2026.1859932

Front Immunol. 2026 ;17 1796161

Immunomodulatory effects of HUC-MSCs therapy: enhancing adaptive and innate immune responses in aging frailty.

Ce Huang, Yingqian Zhu, Xue Gong, Shengyu Feng, Guangying Huo, Hailiang Liu, Hua Jiang, Zhongmin Liu.

Background: Frailty associated with aging, characterized by chronic inflammation and immune dysfunction, poses a significant public health challenge. Human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) exhibit immunomodulatory properties; however, their mechanism of action in frail elderly populations remains unclear. Building on a prior clinical trial investigating HUC-MSCs for elderly frailty (Trial Registration: ClinicalTrials.gov, NCT04314011; PubMed ID: 38679727), this study was conducted to further elucidate the mechanism of action of HUC-MSCs.
Methods: We performed a longitudinal single-cell RNA sequencing (scRNA-seq) study on peripheral blood mononuclear cells (PBMCs) from frail elderly patients before and after HUC-MSCs therapy. Immune cell dynamics were analyzed across multiple time points, and cell-cell communication networks were reconstructed. Spearman correlation analyses were performed to link immune changes with clinical frailty and physical performance metrics.
Results: HUC-MSCs induced a time-dependent recalibration of the immune system. An early, transient expansion of MAIT cells (p=0.049) was followed by a sustained reduction in B cell hyperactivity (p=0.032) and a phenotypic shift in naïve B cells. NK cell cytotoxicity was enhanced (increased GNLY), while NKT cells showed modulated stress-response signatures. Cell-cell communication was reorganized, with the EPHA/NRG pathways highlighting CD4+ TEM, MAIT, and NKT cells as central signaling hubs. Critically, these immunomodulatory changes were quantitatively associated with clinical improvement: reductions in B cell and innate immune subsets correlated with gains in grip strength and gait speed, while regulatory T cell expansion was linked to improved lower-limb function.
Conclusions: HUC-MSCs restore immune homeostasis in aging frailty through sequential, multi-faceted immunomodulation. The association between specific immune remodeling features and functional recovery positions HUC-MSCs as a promising mechanism-based therapy for aging frailty.

Keywords: aging frailty; cell-cell communication; human umbilical cord-derived mesenchymal stem cells (HUC-MSCs); immunosenescence; mucosal-associated invariant T (MAIT) cells; single-cell RNA sequencing

DOI: https://doi.org/10.3389/fimmu.2026.1796161