bims-maitce 2025-06-01 papers

Issue of 2025–06–01
three papers selected by
Andy E. Hogan, Maynooth University

Mucosal Immunol. 2025 May 25. pii: S1933-0219(25)00053-4. [Epub ahead of print]

MAIT cells exacerbate colonic inflammation in a genetically diverse murine model of spontaneous colitis.

Liyen Loh, David J Orlicky, Andrea Spengler, Joanne Domenico, Jared Klarquist, Cassandra Levens, Sofia Celli, Jennifer M Kofonow, Charles E Robertson, Olivier Lantz, Francois Legoux, Daniel N Frank, Jennifer Matsuda, Paul J Norman, Kristine A Kuhn, Joseph Onyiah, Laurent Gapin.

IL-17-producing lymphocytes are involved in both tissue repair and the propagation of inflammation, with their effects highly context-dependent. Mucosal-Associated-Invariant-T-cells (MAIT), a subset of innate-like T cells with features of both Th1 and Th17 lineages, are increasingly recognized for their roles in mucosal immunity. Here, we identified the Collaborative-Cross CC011/Unc strain, which spontaneously develops chronic colitis, as being enriched for MAIT cells. This expansion coincides with an age-related loss of intestinal barrier permeability and colonic inflammation. Microbiota from CC011 mice activated MAIT cells in an MR1-dependent manner and selectively promoted the accumulation of MAIT17 cells in peripheral tissues. Single-cell transcriptomic analyses revealed colon MAIT cells from colitic CC011 mice expressed a pathogenic Th17-like signature, characterized by IL-1 and IL-23 signaling, IL-17A and IFNγ co-expression, and upregulation of IL-23R, features that correlated with inflammatory Ly6Chi monocyte abundance. Genetic deletion of Traj33, essential for MAIT development, significantly reduced colonic inflammation in this model. These findings demonstrate that MAIT cells integrate microbial and cytokine cues to adopt a pathogenic effector phenotype that exacerbates chronic intestinal inflammation.

Keywords: Colitis; Inflammation; MAIT cells; scRNAseq

DOI: https://doi.org/10.1016/j.mucimm.2025.05.006

Biomed Pharmacother. 2025 May 29. pii: S0753-3322(25)00399-3. [Epub ahead of print]188 118205

A systematic review of pharmaceutical targets in the mucosal immune system for treatment of non-intestinal auto-immune diseases.

Boukje C Eveleens Maarse, Amber D Hofstede, Manon A A Jansen, Matthijs Moerland.

The mucosal immune system entails the immune cells located in the body's mucosal surfaces and their mediators. Its function is to balance immune responses to pathogens and tolerance to harmless antigens. Treatment of autoimmune diseases is complicated by adverse events caused by suppression of systemic immunity by immunosuppressive medication. Targeting the mucosal immune system specifically in treating autoimmune diseases could circumvent systemic immune suppression and thereby reduce infection risk. This systematic review aims to provide an overview of pharmaceutical targets in the mucosal immune system, as a starting point in the search for new treatments for extra-intestinal auto-immune diseases. Preclinical and clinical studies were included and categorized into eight target categories: 'immune cells', 'signal transduction', 'inflammatory mediators', 'antibodies', 'microbiome', 'tolerance and mucosal vaccination', 'intestinal barrier' and 'other'. Studies investigating the most promising targets, namely mucosal-associated invariant T cells (MAIT cells) and tolerance induction by mucosal vaccination, are described in more detail. MAIT cells have been shown to play a role in the pathophysiology of various auto-immune diseases, particularly in multiple sclerosis (MS). Although the role of these cells has not yet been established fully, mouse studies show that the antagonism of MAIT cells has the potential to be used in the treatment of auto-immune diseases. Mucosal vaccination has demonstrable effects on the immune system, but treatment regimens and antigens must be improved to demonstrate clinical effects more extensively. This systematic review was registered in PROSPERO under number CRD42023421093.

Keywords: Auto-immune diseases; Microbiome; Mucosal immune system; Mucosal-associated invariant T cells; Pharmacology; Tolerance

DOI: https://doi.org/10.1016/j.biopha.2025.118205

Immunobiology. 2025 May 22. pii: S0171-2985(25)00051-8. [Epub ahead of print]230(3): 152917

MAIT and iNKT cells in tissue homeostasis and repair.

Rafael Almeida Paiva, Marion Salou.

Mucosal-associated invariant T (MAIT) and invariant natural killer T (iNKT) are innate-like T cells, which develop in the thymus through an original developmental program leading to the acquisition of effector memory and tissue targeting phenotypes. Consequently, they become tissue-resident and quickly produce effector molecules both in a T cell receptor (TCR)-dependent manner after stimulation by activating antigens, and in a TCR-independent fashion in response to cytokines. The latter can trigger MAIT and iNKT cells similarly, potentially leading to redundant functions. MAIT and iNKT cells populate most peripheral tissues where they express a wide range of effector modules including immune type 1/2/17, regulatory and repair programs. This endows them with a plethora of functional properties from anti-infectious immunity to regulation of homeostatic processes and tissue repair. In this review, we summarize the current literature on how MAIT and iNKT cells maintain organ homeostasis and contribute to regeneration in vivo, mostly focused on adipose tissue, intestine, lung, liver and skin. Furthermore, we underline TCR- and/or cytokine-dependent mechanisms and potential redundant, non-redundant or even opposing functions.

Keywords: Fibrosis; Innate-like T cells; MAIT cells; Therapeutics; Tissue homeostasis; Tissue repair; iNKT cells

DOI: https://doi.org/10.1016/j.imbio.2025.152917