title: Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma.
abstract: Exposure to inhaled allergens generates T helper 2 (Th2) CD4(+) T cells that contribute to episodes of inflammation associated with asthma. Little is known about allergen-specific Th2 memory cells and their contribution to airway inflammation. We generated reagents to understand how endogenous CD4(+) T cells specific for a house dust mite (HDM) allergen form and function. After allergen exposure, HDM-specific memory cells persisted as central memory cells in the lymphoid organs and tissue-resident memory cells in the lung. Experimental blockade of lymphocyte migration demonstrated that lung-resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4(+) T cells. Investigation into the differentiation of pathogenic Trm cells revealed that interleukin-2 (IL-2) signaling was required for residency and directed a program of tissue homing migrational cues. These studies thus identify IL-2-dependent resident Th2 memory cells as drivers of lung allergic responses.
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hondowicz
authors.affiliation: Center for Lung Biology, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Dowon
authors.initials: D
authors.lastname: An
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Schenkel
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Holly R
authors.initials: HR
authors.lastname: Steach
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Akshay T
authors.initials: AT
authors.lastname: Krishnamurty
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Gladys J
authors.initials: GJ
authors.lastname: Keitany
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Esteban N
authors.initials: EN
authors.lastname: Garza
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Fraser
authors.affiliation: Center for Immunology and Inflammatory Diseases, and Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.affiliation: Center for Lung Biology, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: David
authors.initials: D
authors.lastname: Masopust
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA. Electronic address: mpepper@uw.edu.
authors.forename: Marion
authors.initials: M
authors.lastname: Pepper
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004195:Disease Models, Animal; D005260:Female; D007156:Immunologic Memory / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D007376:Interleukin-2