bims-maitce 2025-03-09 papers

Issue of 2025–03–09
three papers selected by
Andy E. Hogan, Maynooth University

Curr Opin Immunol. 2025 Apr;pii: S0952-7915(25)00018-4. [Epub ahead of print]93 102542

Defenders or defectors: mucosal-associated invariant T cells in autoimmune diseases.

Mitchell Kronenberg, Thomas Riffelmacher.

Mucosal-associated invariant T (MAIT) cells recognize microbial riboflavin metabolites presented by MR1, a major histocompatibility complex class I-like protein. Activated MAIT cells produce cytokines such as interferon gamma (IFNγ), tumor necrosis factor, and interleukin-17; they traffic to sites of infection and participate in protective responses. They are absent in germ-free mice and are dependent on microbes. MAIT cells not only respond to infections but also have been analyzed in various autoimmune diseases. A trend is that in autoimmune disease, MAIT cells are decreased in the circulation and increased and activated or exhausted in the site of inflammation. Despite a possible pathogenic role, publications show MAIT cells also can function in tissue repair. Mouse autoimmune disease models support the presence of both these MAIT cell functions. The signals driving the balance of inflammatory and tissue repair in MAIT cell responses remain to be fully elucidated.

DOI: https://doi.org/10.1016/j.coi.2025.102542

J Biomed Sci. 2025 Mar 01. 32(1): 32

Biological functions and therapeutic applications of human mucosal-associated invariant T cells.

Ying Fang, Yuning Chen, Siyue Niu, Zibai Lyu, Yanxin Tian, Xinyuan Shen, Yan-Ruide Li, Lili Yang.

Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like T lymphocytes that bridge innate and adaptive immunity. Characterized by their semi-invariant T cell receptor (TCR) and abundant localization in mucosal tissues, MAIT cells recognize microbial metabolites, primarily derived from the riboflavin biosynthesis pathway, presented by the major histocompatibility complex (MHC)-related protein 1 (MR1). This interaction, along with co-stimulatory signals, triggers rapid immune responses, including cytokine secretion and cytotoxic activity, highlighting their importance in maintaining immune homeostasis and combating infections. This review provides an in-depth overview of MAIT cell biology, including development, activation pathways, and functional diversity, highlighting their protective roles in immunity, contributions to diseases like cancer and inflammatory bowel disease (IBD), and context-dependent dual functions in health and pathology. This review also highlights the emerging therapeutic potential of MAIT cells in immunotherapy. Their unique TCR specificity, abundance, and tissue-homing properties make them ideal candidates for engineering novel therapies, such as chimeric antigen receptor (CAR)-MAIT cells, targeting infections, cancers, and autoimmune diseases. Challenges like antigen escape, T cell exhaustion, and CAR design optimization must be addressed to enhance clinical efficacy. In summary, MAIT cells are integral to immune function, and their therapeutic potential presents exciting opportunities for the treatment of a wide range of diseases. Further research is essential to unlock the full potential of these versatile immune cells.

Keywords: Allogeneic CAR-T cells; CAR-T cell therapy; Cancer; Immune surveillance; Innate-like lymphocytes; MAIT cells; MR1; Metabolites; Microbiota; Tissue-specific adaptations; Unconventional T cells

DOI: https://doi.org/10.1186/s12929-025-01125-x

Clin Transl Immunology. 2025 ;14(3): e70028

Distinct MAIT cell phenotypes associated with sepsis clinical outcome in emergency department patients.

Johanna Emgård, Iva Filipovic, Christian Unge, Laura M Palma Medina, Åsa Parke, Helena Bergsten, Kirsten Moll, Majda Dzidic, Helena Alpkvist, Hong Fang, Volkan Özenci, Niklas K Björkström, Mattias Svensson, Johan K Sandberg, Kristoffer Strålin, Anna Norrby-Teglund.

Objectives: Rapid diagnosis and intervention are critical for sepsis patient outcomes. However, diagnosis is challenging because of a heterogenic patient group as well as sometimes vague symptoms when the patient presents at the emergency department. Mucosal-associated invariant T (MAIT) cells are rapid responders to infection, but their role and characteristics in the early course of sepsis remain unknown. Here, we evaluate the early MAIT cell characteristics in the blood of patients triggering a clinical sepsis alert system at the emergency department.
Methods: Peripheral blood mononuclear cells were isolated from freshly drawn blood and immediately stained. MAIT cell phenotyping analyses were conducted using multiparameter flow cytometry. All analyses were completed prior to the stratification of patients into sepsis or non-sepsis groups. Soluble factors in plasma were measured using a multiplex assay.
Results: Unsupervised high-dimensional phenotyping identified distinct MAIT cell activation profiles in sepsis and non-sepsis groups. Among sepsis patients, hierarchical clustering of MAIT cell phenotypes separated clinical endotypes into three groups with different infection focus, severity and aetiology. A prominent characteristic of sepsis severity was high expression of CD69 on MAIT cells, which was associated with organ dysfunction, lymphopenia and poor outcome. Plasma levels of IL-12, IL-15, TNF, IFNγ and CXCL10 correlated with the magnitude of MAIT cell activation in sepsis patients.
Conclusions: These clinical endotype-specific MAIT cell phenotypes presenting already in the emergency department are of interest for early patient identification and prognostication in sepsis.

Keywords: MAIT cells; immunophenotyping; sepsis; sepsis endotypes

DOI: https://doi.org/10.1002/cti2.70028