title: MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation.
abstract: The female genital tract (FGT) mucosa is a critically important site for immune defense against microbes. Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell population that recognizes microbial riboflavin metabolite antigens in an MR1-dependent manner. The role of MAIT cells in the FGT mucosa is unknown. Here, we found that MAIT cells and MR1+antigen-presenting cells were present in the upper and lower FGT, with distinct tissue localization of MAIT cells in endometrium vs. cervix. The MAIT cells from the FGT and blood displayed a distinct phenotype with expression of interleukin (IL)-18Rα, CD127, α4β7, PD-1, as well as the transcription factors promyelocytic leukemia zinc finger (PLZF), RORγt, Helios, Eomes, and T-bet. Their expression levels of PLZF and Eomes were lower in the FGT compared with blood. When stimulated with Escherichia coli, MAIT cells from the FGT displayed a bias towards IL-17 and IL-22 expression, whereas blood MAIT cells produced primarily IFN-γ, TNF, and Granzyme B. Furthermore, both FGT- and blood-derived MAIT cells were polyfunctional and contributed to the T-cell-mediated response to E. coli. Thus, MAIT cells in the genital mucosa have a distinct IL-17/IL-22 profile and may have an important role in the immunological homeostasis and control of microbes at this site.
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Gibbs
authors.affiliation: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Leeansyah
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Introini
authors.affiliation: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Paquin-Proulx
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.|Department of Obstetrics and Gynecology, Danderyd Hospital, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Hasselrot
authors.affiliation: Department of Clinical Pathology/Cytology, Capio St Göran Hospital, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Andersson
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Broliden
authors.affiliation: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: J K
authors.initials: JK
authors.lastname: Sandberg
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Tjernlund
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000276:immunology* / Q000473:pathology; D004717:Endometrium / Q000276:immunology* / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000378:metabolism; D009092:Mucous Membrane / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D012256:Riboflavin / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D000942:Antigens, Bacterial; D015395:Histocompatibility Antigens Class I; D020381:Interleukin-17; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012256:Riboflavin; D000097043:Interleukin-22; C094840:MR1 protein, human