title: Irf4 Expression in Thymic Epithelium Is Critical for Thymic Regulatory T Cell Homeostasis.
abstract: The thymus is a primary lymphoid organ required for the induction and maintenance of central tolerance. The main function of the thymus is to generate an immunocompetent set of T cells not reactive to self. During negative selection in the thymus, thymocytes with autoreactive potential are either deleted or differentiated into regulatory T cells (Tregs). The molecular basis by which the thymus allows high-efficiency Treg induction remains largely unknown. In this study, we report that IFN regulatory factor 4 (Irf4) is highly expressed in murine thymic epithelium and is required to prime thymic epithelial cells (TEC) for effective Treg induction. TEC-specific Irf4 deficiency resulted in a significantly reduced thymic Treg compartment and increased susceptibility to mononuclear infiltrations in the salivary gland. We propose that Irf4 is imperative for thymic Treg homeostasis because it regulates TEC-specific expression of several chemokines and costimulatory molecules indicated in thymocyte development and Treg induction.
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia; and uku.haljasorg@ut.ee.
authors.forename: Uku
authors.identifier: 0000-0002-1541-6020
authors.initials: U
authors.lastname: Haljasorg
authors.affiliation: Department of Microbiology and Immunology, KU Leuven, Leuven 3000, Belgium.
authors.forename: James
authors.identifier: 0000-0003-3154-4708
authors.initials: J
authors.lastname: Dooley
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia; and.
authors.forename: Martti
authors.initials: M
authors.lastname: Laan
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia; and.
authors.forename: Kai
authors.initials: K
authors.lastname: Kisand
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia; and.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bichele
authors.affiliation: Department of Microbiology and Immunology, KU Leuven, Leuven 3000, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia; and.
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D006706:Homeostasis; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D017634:Self Tolerance; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000502:physiology; D060168:Thymocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D000099218:Interferon Regulatory Factor-4
chemical_list: D018925:Chemokines; D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4