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REVIEW article

Front. Immunol.
Sec. Mucosal Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1387903
This article is part of the Research Topic Crosstalk Between the GI Redox Environment, Microbiome, and the Immune System View all 4 articles

Gut Redox and Microbiome: Charting the Roadmap to T-Cell Regulation

Provisionally accepted
Sujata Prasad Sujata Prasad 1Shilpi Singh Shilpi Singh 2Samuel Menge Samuel Menge 2Iteeshree Mohapatra Iteeshree Mohapatra 2Stefan Kim Stefan Kim 2Logan Helland Logan Helland 2Gatikrushna Singh Gatikrushna Singh 2*Amar Singh Amar Singh 2*
  • 1 MLM Medical Labs, Memphis, United States
  • 2 University of Minnesota Twin Cities, St. Paul, Minnesota, United States

The final, formatted version of the article will be published soon.

    The gastrointestinal (GI) tract redox environment, influenced by commensal microbiota and bacterial-derived metabolites, is crucial in shaping T-cell responses. Specifically, metabolites from gut microbiota (GM) exhibit robust anti-inflammatory effects, fostering the differentiation and regulation of CD8 + tissue-resident memory (TRM) cells, mucosalassociated invariant T (MAIT) cells, and stabilizing gut-resident Treg cells. Nitric oxide (NO), a pivotal redox mediator, emerges as a central regulator of T-cell functions and gut inflammation. NO impacts the composition of the gut microbiome, driving the differentiation of pro-inflammatory Th17 cells and exacerbating intestinal inflammation, and supports Treg expansion, showcasing its dual role in immune homeostasis. This review delves into the complex interplay between GI redox balance and GM metabolites, elucidating their profound impact on T-cell regulation. Additionally, it comprehensively emphasizes the critical role of GI redox, particularly reactive oxygen species (ROS) and NO, in shaping T-cell phenotype and functions. These insights offer valuable perspectives on disease mechanisms and potential therapeutic strategies for conditions associated with oxidative stress. Understanding the complex cross-talk between GI redox, GM metabolites, and T-cell responses provides valuable insights into potential therapeutic avenues for immune-mediated diseases, underscoring the significance of maintaining GI redox balance for optimal immune health.

    Keywords: Redox, T-cells, Gut microbiome, Reactive Oxygen Species, Nitric Oxide, Metabolites, Short chain Fatty acid, Th1 cells, Th17 cells, Treg cells, Resident Memory T-cells, Mucosal Associated T-cells, Immune regulation Antigen-presenting cells, ARE, antioxidant response element, ATP: adenosine triphosphate, BHLHE40: Basic Helix-Loop-Helix Family Member E40, Blimp-1: B lymphocyte-induced maturation protein-1, Eomes: Eomesodermin, ER: endoplasmic reticulum, ETC: Electron transport chain

    Received: 18 Feb 2024; Accepted: 31 Jul 2024.

    Copyright: © 2024 Prasad, Singh, Menge, Mohapatra, Kim, Helland, Singh and Singh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Gatikrushna Singh, University of Minnesota Twin Cities, St. Paul, 55108, Minnesota, United States
    Amar Singh, University of Minnesota Twin Cities, St. Paul, 55108, Minnesota, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.