bims-maitce 2026-06-28 papers

Issue of 2026–06–28
three papers selected by
Andy E. Hogan, Maynooth University

J Gastroenterol. 2026 Jun 24.

Mucosal-associated invariant T cells promote PDAC progression via TL1A-CSF-1 axis.

Longyun Ye, Qinglin Fei, Tianjiao Li, Huiyi Ou, Shuai Wang, Yiting Zhang, Yi Zhou, Xianjun Yu, Kaizhou Jin, Weiding Wu.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells have been implicated in several malignancies, but their role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study aimed to characterize the presence, phenotype, and functional role of MAIT cells in PDAC and explore the underlying regulatory mechanisms.
METHODS: We analyzed human PDAC tissue samples using single-cell RNA sequencing and flow cytometry to evaluate MAIT cell abundance and phenotype. Functional studies were performed in MR1-deficient (Mr1-/-) mice to assess the impact of MAIT cell deficiency on tumor-associated macrophage polarization. Cytokine profiling and signaling analyses were used to investigate mechanisms of MAIT cell activation within the tumor microenvironment.
RESULTS: MAIT cells were significantly enriched in PDAC tissues and associated with poor patient survival. Further studies inMR1-deficient (Mr1-/-) mice demonstrated that the absence of MAIT cells markedly attenuated M2 macrophage polarization. Mechanistically, tissue-resident MAIT cells secreted higher levels of CSF-1 versus circulating subsets. This phenomenon suggests that MAIT cells may be reprogrammed by the tumor microenvironment. Building on this, we discovered that Ttumor-derived TL1A activated MAPK signaling in MAIT cells, potentiating CSF-1 secretion.
CONCLUSIONS: Our findings reveal a novel TL1A-MAIT-CSF-1 axis that drives immunosuppression in PDAC by reprogramming innate immune responses. Targeting MAIT cells or TL1A signaling may represent a promising therapeutic strategy to improve immunotherapy efficacy in PDAC.

Keywords: CSF-1; Mucosal-associated invariant T (MAIT); PDAC; TL1A

DOI: https://doi.org/10.1007/s00535-026-02468-4

Immunol Cell Biol. 2026 Jun 23.

4-1BB Expression and Signaling Regulates MAIT Cell Activation and Effector Functions.

Lamichhane R, Williams J, Tirand C, Fouillé R, Wedlock LE, Poudel A, Webley Mc, Hannaway Rf, Ussher Je.

Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells that recognize microbe-derived riboflavin metabolites presented by MR1. Upon recognition, they become activated, produce proinflammatory cytokines, chemokines, and cytotoxic molecules. MAIT cells are also activated by cytokines independently of T cell receptor (TCR) engagement; however, these two signals can also act in concert to fine-tune MAIT cell functions. Additionally, multiple other co-stimulatory signals have also been reported that can boost MAIT cell effector responses to TCR or cytokine stimulation. However, a comprehensive study exploring the role of surface-bound TNF receptor superfamily (TNFRSF) molecule 4-1BB, well known for its co-stimulatory function during conventional T cell activation, is lacking in the context of MAIT cells. In this study, we show that 4-1BB is the earliest and most highly expressed TNFRSF co-stimulatory molecule on MAIT cells upon activation by Escherichia coli, with expression seen as early as 6 h where it was predominantly MR1 mediated. 4-1BB expression on MAIT cells following late activation was due to both TCR signaling and cytokine signaling. We found marked differences in MAIT cell activation and cytokine expression between 4-1BB+ and 4-1BB- MAIT cells suggesting 4-1BB expression on MAIT cells is associated with functional superiority. By blocking 4-1BB signaling or coculturing with a 4-1BBL overexpressing cell line, we demonstrated an important role of co-stimulation via 4-1BB in MAIT cells during activation. Expression and signaling via 4-1BB also enhanced T-bet and Blimp1 expression. In summary, our study confirms a role for 4-1BB signaling during MAIT cell activation.

Keywords: 4‐1BB; MAIT cells; T cell receptor; activation; effector functions; signaling

DOI: https://doi.org/10.1111/imcb.70142

Front Immunol. 2026 ;17 1809165

Mechanistic insights into how gut homeostasis and immune-system crosstalk shape ankylosing spondylitis.

Jiawen Li, Xingwen Xie.

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease that primarily affects the axial skeleton and entheseal structures. Although the role of HLA-B27 is well established, AS pathogenesis is multifactorial, and accumulating evidence suggests that disruption of intestinal homeostasis and the gut-joint axis may contribute to disease pathobiology. AS-associated gut dysbiosis is characterized by reduced microbial diversity and compositional alterations that may be associated with mucosal immune activation, increased intestinal permeability, and systemic inflammatory priming. Mechanistically, altered microbial signals and barrier dysfunction may converge on key immunological pathways, including the IL-23/IL-17 axis, and may promote the activation or trafficking of innate-like lymphocytes, such as MAIT cells, γδ T cells, and ILC3s, thereby contributing to inflammation and abnormal bone remodeling. In addition to community structure, microbial metabolites, including short-chain fatty acids and tryptophan-derived indole metabolites, help regulate epithelial integrity and immunoregulatory homeostasis; their perturbation may favor pro-inflammatory immune programs relevant to AS. This review summarizes recent evidence on dysbiosis, barrier dysfunction, and immunometabolic signaling in the gut-joint axis, while critically distinguishing established immune-targeted therapies from experimental microbiota-directed and combination strategies.

Keywords: ankylosing spondylitis; gut microbiota; gut – joint axis; intestinal barrier dysfunction; microbial metabolites; mucosal immunity

DOI: https://doi.org/10.3389/fimmu.2026.1809165