MAIT Cell Homing in Intestinal Homeostasis and Inflammation

Overview

Journal Sci Adv

Date 2025 Feb 7

PMID 39919191

Authors

Zhengyu Wu

Xingchi Chen

Fei Han

Edwin Leeansyah

Affiliations

Soon will be listed here.

Abstract

Mucosa-associated invariant T (MAIT) cells are a large population of unconventional T cells widely distributed in the human gastrointestinal tract. Their homing to the gut is central to maintaining mucosal homeostasis and immunity. This review discusses the potential mechanisms that guide MAIT cells to the intestinal mucosa during homeostasis and inflammation, emphasizing the roles of chemokines, chemokine receptors, and tissue adhesion molecules. The potential influence of the gut microbiota on MAIT cell homing to different regions of the human gut is also discussed. Last, we introduce how organoid technology offers a potentially valuable approach to advance our understanding of MAIT cell tissue homing by providing a more physiologically relevant model that mimics the human gut tissue. These models may enable a detailed investigation of the gut-specific homing mechanisms of MAIT cells. By understanding the regulation of MAIT cell homing to the human gut, potential avenues for therapeutic interventions targeting gut inflammatory conditions such as inflammatory bowel diseases (IBD) may emerge.

References

Moles L, Gomez M, Heilig H, Bustos G, Fuentes S, de Vos W . Bacterial diversity in meconium of preterm neonates and evolution of their fecal microbiota during the first month of life. PLoS One. 2013; 8(6):e66986. PMC: 3695978. DOI: 10.1371/journal.pone.0066986. View

Tsukamoto K, Deakin J, Marshall Graves J, Hashimoto K . Exceptionally high conservation of the MHC class I-related gene, MR1, among mammals. Immunogenetics. 2012; 65(2):115-24. DOI: 10.1007/s00251-012-0666-5. View

Germain L, Veloso P, Lantz O, Legoux F . MAIT cells: Conserved watchers on the wall. J Exp Med. 2024; 222(1). PMC: 11514058. DOI: 10.1084/jem.20232298. View

Tominaga K, Yamagiwa S, Setsu T, Kimura N, Honda H, Kamimura H . Possible involvement of mucosal-associated invariant T cells in the progression of inflammatory bowel diseases. Biomed Res. 2017; 38(2):111-121. DOI: 10.2220/biomedres.38.111. View

Leeansyah E, Hey Y, Sia W, Jia Ng J, Gulam M, Boulouis C . MR1-Restricted T Cells with MAIT-like Characteristics Are Functionally Conserved in the Pteropid Bat . iScience. 2020; 23(12):101876. PMC: 7736909. DOI: 10.1016/j.isci.2020.101876. View

Paroni M, Leccese G, Ranzani V, Moschetti G, Chiara M, Perillo F . An Intestinal Th17 Subset is Associated with Inflammation in Crohn's Disease and Activated by Adherent-invasive Escherichia coli. J Crohns Colitis. 2023; 17(12):1988-2001. PMC: 10798865. DOI: 10.1093/ecco-jcc/jjad119. View

Winter S, Baumler A . Gut dysbiosis: Ecological causes and causative effects on human disease. Proc Natl Acad Sci U S A. 2023; 120(50):e2316579120. PMC: 10722970. DOI: 10.1073/pnas.2316579120. View

Proudfoot A . Chemokine receptors: multifaceted therapeutic targets. Nat Rev Immunol. 2002; 2(2):106-15. PMC: 7097668. DOI: 10.1038/nri722. View

Sharma A, Lawry S, Klein B, Wang X, Sherer N, Zumwalde N . LFA-1 Ligation by High-Density ICAM-1 Is Sufficient To Activate IFN-γ Release by Innate T Lymphocytes. J Immunol. 2018; 201(8):2452-2461. PMC: 6179935. DOI: 10.4049/jimmunol.1800537. View

10.

Li S, Simoni Y, Becht E, Loh C, Li N, Lachance D . Human Tumor-Infiltrating MAIT Cells Display Hallmarks of Bacterial Antigen Recognition in Colorectal Cancer. Cell Rep Med. 2020; 1(3):100039. PMC: 7659584. DOI: 10.1016/j.xcrm.2020.100039. View

11.

Voillet V, Buggert M, Slichter C, Berkson J, Mair F, Addison M . Human MAIT cells exit peripheral tissues and recirculate via lymph in steady state conditions. JCI Insight. 2018; 3(7). PMC: 5928862. DOI: 10.1172/jci.insight.98487. View

12.

Ju J, Cho Y, Park K, Kwak H, Jin H, Park S . Activation, Deficiency, and Reduced IFN-γ Production of Mucosal-Associated Invariant T Cells in Patients with Inflammatory Bowel Disease. J Innate Immun. 2020; 12(5):422-434. PMC: 7506267. DOI: 10.1159/000507931. View

13.

Sundstrom P, Ahlmanner F, Akeus P, Sundquist M, Alsen S, Yrlid U . Human Mucosa-Associated Invariant T Cells Accumulate in Colon Adenocarcinomas but Produce Reduced Amounts of IFN-γ. J Immunol. 2015; 195(7):3472-81. DOI: 10.4049/jimmunol.1500258. View

14.

Suliman S, Murphy M, Musvosvi M, Gela A, Meermeier E, Geldenhuys H . MR1-Independent Activation of Human Mucosal-Associated Invariant T Cells by Mycobacteria. J Immunol. 2019; 203(11):2917-2927. PMC: 6859375. DOI: 10.4049/jimmunol.1900674. View

15.

Ollila T, Sahin I, Olszewski A . Mogamulizumab: a new tool for management of cutaneous T-cell lymphoma. Onco Targets Ther. 2019; 12:1085-1094. PMC: 6369856. DOI: 10.2147/OTT.S165615. View

16.

Griffith J, Sokol C, Luster A . Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol. 2014; 32:659-702. DOI: 10.1146/annurev-immunol-032713-120145. View

17.

Jabeen M, Hinks T . MAIT cells and the microbiome. Front Immunol. 2023; 14:1127588. PMC: 9995591. DOI: 10.3389/fimmu.2023.1127588. View

18.

Jimenez E, Marin M, Martin R, Odriozola J, Olivares M, Xaus J . Is meconium from healthy newborns actually sterile?. Res Microbiol. 2008; 159(3):187-93. DOI: 10.1016/j.resmic.2007.12.007. View

19.

Tanoue T, Morita S, Plichta D, Skelly A, Suda W, Sugiura Y . A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019; 565(7741):600-605. DOI: 10.1038/s41586-019-0878-z. View

20.

Christopherson 2nd K, Uralil S, Porecha N, Zabriskie R, Kidd S, Ramin S . G-CSF- and GM-CSF-induced upregulation of CD26 peptidase downregulates the functional chemotactic response of CD34+CD38- human cord blood hematopoietic cells. Exp Hematol. 2006; 34(8):1060-8. DOI: 10.1016/j.exphem.2006.03.012. View