bims-maitce 2026-03-15 papers

Issue of 2026–03–15
four papers selected by
Andy E. Hogan, Maynooth University

Immune Netw. 2026 Feb;26(1): e8

Dual Roles of MAIT Cells in the Tumor Microenvironment: Implications for Cancer Immunity and Therapy.

Mucosal-associated invariant T (MAIT) cells are innate T cells that recognize riboflavin metabolites with canonical TCRs and develop in the thymus as memory cells. They account for 1%-10% of peripheral blood T cells in humans and are frequently observed within the tumor microenvironment (TME). However, their functional roles remain controversial. In certain tumors, infiltrated MAIT cells upregulate cytotoxic receptor NKG2D and effector cytokines, including IFNγ, TNFα, and granzyme, contributing to tumor control. In other settings, they exhibit reduced cytokine production, increased expression of inhibitory receptors such as PD-1, CTLA-4, and TIM-3, and are associated with unfavorable clinical outcomes. These discrepancies are influenced by the source of MR1 ligands, cytokine composition, and metabolic conditions within the TME. Meanwhile, due to the innate cytotoxicity and lack of alloreactivity, MAIT cells are attractive candidates for cellular immunotherapy. This review summarizes the functional dichotomy of MAIT cells in cancers and outlines strategies to harness their anti-tumor properties.

Keywords: Immunotherapy; Mucosal-associated invariant T cells; Tumor

DOI: https://doi.org/10.4110/in.2026.26.e8

Cell Prolif. 2026 Mar 10. e70194

Single Cell Multi-Omics Revealing the Important Role of MR1 Mediated MAIT Cells in Maintaining Rejection for Liver Transplantation.

Hailun Cai, Xinqiang Li, Xin Zhou, Xueteng Wang, Zhuoyu Jia, Ruidong Ding, Yurong Luo, Ye Wang, Shipeng Li, Wenxing Sun, Dongxing Wu, Dahong Teng, Kai Zhao, Guanghui Pei, Jinzhen Cai, Bin Wu.

Mucosal-associated invariant T (MAIT) cells, representing one of the most abundant subsets of unconventional T cells, have been shown to play a significant role in regulating immune responses. However, their immunoregulatory roles in the context of liver transplantation (LT) immunity remain largely undefined. To address this, we conducted single-cell RNA/TCR sequencing, flow cytometry, and multiplex immunohistochemical (mIHC) assays to identify the proportion and characteristics of CD8+ MAIT cells in humans and mice following liver transplantation. We found that CD8+ MAIT cells were prominently represented in the single-cell CD8 profiles of human transplanted livers, demonstrating strong signalling associations with macrophages, whilst the fractional populations of MAIT1 and MAIT17 were distinctly clustered. In parallel, the proportion of CD8+ MAIT cells was significantly elevated in mouse LT models, revealing a dynamic trend where percentages increased at 1 and 2 weeks post-transplant, peaking at 3 weeks. Furthermore, using established MR1 knockout (MR1KO) LT mice, we observed that mice lacking MAIT cells exhibited milder rejection responses, indicating that MR1 mediates rejection by influencing the remodelling of the TCR repertoire after transplantation. Collectively, our study reveals that MAIT cells play a critical role in LT rejection, as MR1KO alleviated inflammatory responses and mitigated rejection via TCR repertoire remodelling. By mapping the dynamic changes of MAIT cells throughout the rejection process, these findings lay the groundwork for further investigations into the role of these cells in transplant immunity.

Keywords: graft rejection; liver transplantation; major histocompatibility complex class I related protein‐1; mucosal‐associated invariant T cells

DOI: https://doi.org/10.1111/cpr.70194

Front Immunol. 2026 ;17 1745933

Single-cell analysis reveals immune remodeling of monocytes, NK cells, T cell exhaustion, and Galectin-9-associated depletion of gamma delta and mucosal-associated invariant T cells in Long COVID with ME/CFS.

Shima Shahbaz, Najmeh Bozorgmehr, Amirhossein Rahmati, Amal Abouda, Hussain Syed, Mohammed Osman, Shokrollah Elahi.

Introduction: The cellular mechanisms underlying Long COVID (LC) associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain poorly understood.
Methods: We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells collected 12 months after acute COVID-19 infection from female individuals with LC-ME/CFS and recovered (R) individuals. Comparative analysis was also performed using publicly available scRNA-seq datasets from idiopathic ME/CFS patients.
Results: Based on transcriptional signatures, LC-ME/CFS patients exhibited a marked reduction in naïve CD4+ and CD8+ T cells, regulatory T cells, MAIT cells, and γδ T cells, accompanied by an expansion of effector T cells. NK cells displayed reduced frequency and altered activation-associated transcriptional factors, consistent with impaired cytotoxic potentials. B cells in LC patients exhibited gene expression profiles indicative of heightened activation, while plasma cells revealed a distinct transcriptional subset expressing NK-associated genes. Platelets and low-density neutrophils were expanded and exhibited enrichment of activated-related transcripts. Monocyte subsets demonstrated transcriptional skewing characterized by reduced expression of phagocytosis-associated genes and increased expression of pro-inflammatory cytokine-related genes/pathways. In contrast, idiopathic ME/CFS patients exhibited less pronounced immune alterations at the transcriptional level: while T cell activation was evident, there was no reduction in MAIT or NK cells, nor signs of T cell exhaustion. Notably, FOXP3 expression was upregulated, and B cells and platelets demonstrated dysregulated signatures in idiopathic ME/CFS. Mechanistically, we identify Galectin-9-TIM-3 interaction as a potential pathway driving γδ and MAIT cell depletion in LC.
Conclusion: Our results reveal extensive peripheral immune remodeling in LC-ME/CFS, distinct from idiopathic ME/CFS, and support a model of chronic immune activation and dysregulation. Our findings offer a cellular framework for understanding LC pathogenesis and point to potential biomarkers and therapeutic targets for intervention.

Keywords: Reelin; TIM-3; Tregs; olfactory receptors; platelets; sex hormone receptors

DOI: https://doi.org/10.3389/fimmu.2026.1745933

J Med Biochem. 2026 Jan 28. 45(1): 133-140

Diagnostic value of mucosal-associated invariant T+ cells combined with inflammatory factors in differentiating chronic rhinosinusitis subtypes with or without nasal polyps.

Yilong Wang, Yongjun Feng, Jie Song, Zhonglin Mou.

Background: The present study attempted to analyze the effect of mucosal-associated invariant T (MAIT) combined with inflammatory factors in identifying chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) that provides a clinical reference.
Methods: In this retrospective study, we enrolled 56 CRSsNP patients, 68 CRSwNP patients, and 64 healthy controls. Flow cytometry was used to detect the frequency of peripheral blood MAIT+ cells (MAIT+). Serum levels of hs-CRP, IL-ip, and IL-6 were measured by ELISA and automatic blood cell analyzer, and their correlations with MAIT cell alterations were analyzed. The diagnostic effect of MAIT+ combined with hs-CRP IL-ip, and IL-6 on CRS was analyzed using ROC curves.
Results: Both CRSsNP and CRSwNP patients exhibited significantly reduced MAIT+ frequencies compared to controls (P< 0.05), with CRSwNP showing the most pronounced decrease (P < 0.0 5). MAIT+ frequency was inversely correlated with hs-CRP IL-ip, and IL-6 in CRS patients. ROC analysis demonstrated that MAIT+ effectively discriminated CRSsNP (AU C= 0.793) and CRSwNP (AU C= 0.863) from healthy individuals (P< 0.01). After combined with inflammatory factors, the diagnostic effect of MAIT+ combined inflammatory factors on CRSsNP (AU C= 0.933) and CRSwNP (AU C= 0.939) was further improved.
Conclusions: Detection of MAIT+ combined with inflammatory factors may provide potential biomarkers for CRS subtype identification.

Keywords: biomarker; chronic rhinosinusitis; inflammatory factors; mucosal-associated invariant T cells; nasal polyps

DOI: https://doi.org/10.5937/jomb0-59840