Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Lung inflammatory injury and tissue repair (Jul 2023)
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation
Yue Cui, … , Claire Soudais, Olivier Lantz
Yue Cui, … , Claire Soudais, Olivier Lantz
Published October 12, 2015
Citation Information: J Clin Invest. 2015;125(11):4171-4185. https://doi.org/10.1172/JCI82424.
View: Text | PDF
Research Article Immunology

Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

  • Text
  • PDF
Abstract

Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%–10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≈0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4–CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7–). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.

Authors

Yue Cui, Katarzyna Franciszkiewicz, Yvonne K. Mburu, Stanislas Mondot, Lionel Le Bourhis, Virginie Premel, Emmanuel Martin, Alexandra Kachaner, Livine Duban, Molly A. Ingersoll, Sylvie Rabot, Jean Jaubert, Jean-Pierre De Villartay, Claire Soudais, Olivier Lantz

×

Figure 1

MAIT abundance in mouse is determined by genetic background rather than a limited microbiota.

Options: View larger image (or click on image) Download as PowerPoint
MAIT abundance in mouse is determined by genetic background rather than ...
(A) Normalized Vα19-Jα33 mRNA levels in the LP of the progeny of GF Mr1+ Tap–/– Ii–/– breeding pairs reconstituted or not with human microbiota. Mr1+ or Mr1–/– Tap–/– Ii–/– SPF mice are shown as controls. (B) Normalized Vα19-Jα33 mRNA expression in the MLNs of B6, PWK, CAST, F1 (B6 × CAST), and N2 (F1 × B6). (C) Manhattan plot of SNP call significance (–log10[P]) of MAIThi versus MAITlo (BC2 or BC3) ordered by chromosomal location. (D) Normalized Vα19-Jα33 mRNA expression in the MLNs of F2 (F1 × F1) mice, grouped by genotype of the MAIThi locus: B6/B6, Het, CAST/CAST. (E) Genomic map of the chromosome 14 TCR-α region encompassing the MAITCAST locus (boxed).

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts