bims-maitce 2026-02-08 papers

Issue of 2026–02–08
three papers selected by
Andy E. Hogan, Maynooth University

Clin Kidney J. 2026 Feb;19(2): sfaf366

Mucosal-associated invariant T cells and the gut-kidney axis: a review.

Xu Zhang, Jiaqiang Wang, Yunxuan He, Xiang Xiao, Junming Fan, Xin Ma.

Mucosal-associated invariant T (MAIT) cells are a distinct subset of innate-like lymphocytes that bridge microbial homeostasis and tissue immunity. These evolutionarily conserved cells are activated via the recognition of microbial metabolites presented by the MR1 molecule and establish stable residency in the kidney, where they profoundly influence local immune-metabolic processes. There is growing interest in the robust regulatory capacities of MAIT cells in renal physiology and pathology. This review systematically delineates their paradoxical roles in kidney diseases. Under specific conditions, they exert protective functions by suppressing inflammation and maintaining tissue homeostasis. Conversely, in distinct microenvironments, they adopt a pro-inflammatory phenotype, exacerbating pathological progression through the release of inflammatory cytokines and cytotoxic effector functions. The gut-kidney axis serves as a critical regulatory hub, wherein dysbiosis-derived signals can significantly amplify the renal impact of MAIT cells. Focusing on clinical translation, we provide an in-depth exploration of innovative strategies targeting MAIT cells, including adoptive cell therapy, receptor-targeting agents, and microbiome reconstruction. These approaches position MAIT cells as promising therapeutic targets for a new generation of immune-mediated kidney diseases.

Keywords: MAIT cell; gut–kidney axis; immune regulation; renal disease; therapeutic targets

DOI: https://doi.org/10.1093/ckj/sfaf366

Front Immunol. 2025 ;16 1656167

Flavin and deazaflavin biosynthesis in mycobacteria: relevance to physiology, implications for drug discovery, MR-1 antigenicity, and vaccine development.

Nurudeen Oketade, Melissa D Chengalroyen, Dylan Kain, David M Lewinsohn, Karen M Dobos.

Flavin and deazaflavin biosynthesis are highly conserved pathways in mycobacteria, including in Mycobacterium tuberculosis (M.tb). Flavin biosynthesis on one hand is required to produce FMN and FAD, two essential cofactors required to support the flavin intensive lifestyle of mycobacteria. Deazaflavin biosynthesis on the other hand provides F420, an important cofactor used by mycobacteria to curtail antimicrobial and immunological stressors. Given these crucial roles for mycobacterial survival and virulence, these connected pathways have been a recent focus of drug discovery efforts. In addition to providing these important cofactors, studies have shown that the intermediates of this pathway are required to produce metabolic antigens presented by the MHC class I related protein (MR1) molecule in mycobacteria. T cells restricted by the MR1 molecule, which includes Mucosal-associated invariant T cells (MAITs), have also been shown to play a key role during M.tb infection. These findings have made MR1 restricted T cells a prime target for vaccine development. In this review, we focus on what is known about flavin and deazaflavin synthesis pathways in M.tb and other mycobacteria and the distinct features in these species. We also cover the role of these pathways in the physiology of mycobacteria, as well as the status of small molecule inhibitors targeting this pathway. We discuss the current understanding of MR1 immunology in M.tb infection, based on studies in both animal models and humans. Additionally, we highlight recent findings on the diverse repertoire of MR1 T cell receptors that expand during infection and the current status of the MR1 ligandome. Most importantly, we discuss current gaps in understanding the importance of these pathways and explore how this knowledge could drive the development of therapeutics for mycobacterial diseases by targeting these pathways and protective MR1-restricted T cell responses.

Keywords: MR1T and MAIT cells; flavin and deazaflavin; flavin sequestration; mycobacteria; therapeutics; tuberculosis; vaccines

DOI: https://doi.org/10.3389/fimmu.2025.1656167

J Infect Dis. 2026 Feb 05. pii: jiag078. [Epub ahead of print]

Single-Cell Sequencing Reveals Varying Cell-Mediated Immunity Profiles in Individuals with Distinct Antibody Responses Following Ad5-nCoV Booster.

Conghui Liao, Yan Long, Renyun Zha, Lin Cai, Xin Guan, Junda Bai, Yuxiang Ye, Xiaokang Li, Weiya Mao, Jiani Wu, Jiahai Lu, Zunfu Ke, Cheng Guo.

BACKGROUND: Vaccination is critical for controlling infectious diseases, however, assessing efficacy solely through neutralizing antibody titers oversimplifies immune protection. The cellular and molecular mechanisms driving variable vaccine-induced immune responses remain underexplored, limiting comprehensive vaccine evaluation.
METHODS: Using single-cell sequencing, we profiled and compared cellular dynamic, transcriptomic profiles, immune repertoire and cellular communication in vaccine recipients with high and low antibody titers following Ad5-nCoV booster using PBMC samples collected from a cohort of 144 participants.
RESULTS: Cellular profiling revealed no significant changes in most immune cell subsets. However, high response groups exhibited increased cytotoxic CD8+ lymphocytes (CD8+ CTL) and natural killer T cells (NKT), with reduced CD8+ mucosal-associated invariant T cells (CD8+ MAIT). These groups showed upregulated immune and effector genes, downregulated pro-inflammatory genes, and elevated inhibitory gene expression in clonal NK cells, accompanied by enhanced CD8+ T cell clonal expansion. Additionally, the VJ gene usage of B and T cells in high response groups showed biased patterns, with preferential expression of IGLJ3, IGKJ3, IGHV3-33 and IGHJ4 in B cells, and TRAV27, TRAJ33, TRBV9 and TRBJ2-7 in T cells. Cell communication also indicated balanced pro- and anti-inflammatory cytokine expression in high response groups.
CONCLUSIONS: These findings elucidate the cellular and molecular mechanisms underlying robust immune responses to the Ad5-nCoV booster, highlighting the critical role of cellular immunity. By integrating humoral and cellular insights, this study offers a new perspective of comprehensive framework for evaluating vaccine efficacy.

Keywords: booster immunization; immune response; single cell sequencing

DOI: https://doi.org/10.1093/infdis/jiag078