title: Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation.
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.forename: Yue
authors.initials: Y
authors.lastname: Cui
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Franciszkiewicz
authors.forename: Yvonne K
authors.initials: YK
authors.lastname: Mburu
authors.forename: Stanislas
authors.initials: S
authors.lastname: Mondot
authors.forename: Lionel
authors.initials: L
authors.lastname: Le Bourhis
authors.forename: Virginie
authors.initials: V
authors.lastname: Premel
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Martin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kachaner
authors.forename: Livine
authors.initials: L
authors.lastname: Duban
authors.forename: Molly A
authors.initials: MA
authors.lastname: Ingersoll
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rabot
authors.forename: Jean
authors.initials: J
authors.lastname: Jaubert
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: De Villartay
authors.forename: Claire
authors.initials: C
authors.lastname: Soudais
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D005856:Germ-Free Life; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D051741:Kruppel-Like Transcription Factors / Q000032:analysis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000166:cytology; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064307:Microbiota; D015778:Minor Histocompatibility Antigens; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000032:analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018121:Receptors, Cytokine / Q000032:analysis; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology
chemical_list: D015395:Histocompatibility Antigens Class I; D051741:Kruppel-Like Transcription Factors; D008222:Lymphokines; D015778:Minor Histocompatibility Antigens; C490628:Mr1 protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018121:Receptors, Cytokine; C513267:Zbtb16 protein, mouse