bims-maitce 2026-05-17 papers

Issue of 2026–05–17
three papers selected by
Andy E. Hogan, Maynooth University

Geroscience. 2026 May 16.

Intestinal T cells in aging: implications for gut barrier integrity and inflammaging.

Christina M Stevens, Cecilia R Schaaf, Theodore M DeConne, Kylie Kavanagh.

Aging is accompanied by a progressive decline in intestinal barrier integrity, resulting in increased permeability to luminal microbes and microbial products and contributing to chronic low-grade inflammation ("inflammaging"). While epithelial and microbial changes have been extensively studied, the role of intestinal T cells as active regulators of barrier homeostasis during aging remains underappreciated. The gut harbors the largest population of T cells in the body, including diverse conventional and unconventional subsets that directly shape epithelial differentiation, mucus production, antimicrobial defense, and tight junction organization through cytokine-mediated signaling. In this review, we synthesize current evidence linking age-related alterations in intestinal T-cell composition and function to epithelial barrier decline. We focus on key T-cell subsets including Th1, Th17, Th22, regulatory T cells, γδ T cells, mucosal-associated invariant T (MAIT) cells, and intraepithelial lymphocytes, and discuss how aging-associated shifts in their cytokine profiles may disrupt the balance between barrier maintenance, repair, and inflammation. We further examine how T-cell dysfunctions characteristic of aging, including senescent-like and exhausted phenotypes, may exacerbate epithelial injury, microbial translocation, and systemic immune activation. Insights from age-accelerated conditions such as HIV/SIV infection and inflammatory bowel disease are used to inform emerging models of T-cell-driven barrier decline in older adults.

Keywords: Aging; Immunosenescence; Inflammaging; Intestinal barrier function; Microbial translocation; T cells

DOI: https://doi.org/10.1007/s11357-026-02292-x

Arthritis Rheumatol. 2026 May 11.

T cells, the next big target in axSpA?

Mansi K Aparnathi, Nigil Haroon.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by complex immune dysregulation, with T cells playing a central role in its pathogenesis. In this review we synthesize current knowledge on diverse T cell subsets in axSpA, their pathogenic mechanisms, and emerging therapeutic strategies targeting these cells. We highlight conventional αβ T cell receptor (TCR) expressing CD8+ T cells, CD4+ Th17and Treg cells, and CD103+CD49a+ tissue-resident memory (TRM) integrin expressing (InEx) T cells in axSpA initiation and progression. Innate-like T cell subsets, including γδ T cells, mucosal-associated invariant T (MAIT) cells, and invariant natural killer T (iNKT) cells alongwith innate lymphoid cells (ILC3s, though not T cells), contribute substantially via interlukin-17 (IL-17) production via IL-23, driving inflammation and tissue damage. We discuss complex milieu of cytokines in T cell-mediated inflammation, offering potential explanations for inefficacy of some cytokine inhibitors. We explore alternative drivers of inflammation and their implications for developing more effective therapies targeting T cells in axSpA, either directly via anti-TRBV9 antibody therapy or janus kinase (JAK) inhibition or indirectly by inhibiting mediators such as IL-17 and TNF. This complex interplay of T cell subsets in disease pathogenesis underscores the need for research to develop more targeted treatments, opening new avenues for personalized therapies and combination approaches that address multiple aspects of the inflammatory cascade in axSpA.

DOI: https://doi.org/10.1002/art.70221

Sci China Life Sci. 2026 Apr 30.

Human MAITregs possess diverse TCR repertoires and are functionally supported by glycolysis.

Maoyu Tang, Xinying Li, Xudong Yang, Changfeng Zhao, Yuwei Zhang, Sanwei Chen, Zhenghui Ye, Liujin Hou, Yusheng Chen, Rong Lv, Hongchuan Zhao, Xiaowen Cheng, Hua Wang, Li Bai, Sicheng Fu.

Mucosal-associated invariant T (MAIT) regulatory cells (MAITregs) represent a specialized subset with immunosuppressive functions, yet their properties and molecular basis are largely unknown. We demonstrate that MAITregs, while sharing T cell receptor (TCR) repertoires with conventional MAIT cells, undergo selective clonal expansion during in vitro generation, leading to biased V(D)J profiles and restricted CDR3 diversity. Moreover, integrated transcriptomics revealed that MAITregs preferred glycolysis, which was supported by chromatin remodeling at glycolytic gene loci. Functionally, glycolysis in MAITregs favored their IL-10 production but inhibited Th1 cytokines, whereas oxidative phosphorylation (OXPHOS) promoted their Th1/Th17 cytokines. Our study defines MAITregs as a clonally expanded population whose regulatory potency is strictly governed by cellular metabolism.

Keywords: diverse TCR repertoires; glycolysis; human MAITregs

DOI: https://doi.org/10.1007/s11427-025-3259-0