title: IL-33-responsive lineage- CD25+ CD44(hi) lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs.
abstract: Innate immunity provides the first line of response to invading pathogens and a variety of environmental insults. Recent studies identified novel subsets of innate lymphoid cells that are capable of mediating immune responses in mucosal organs. In this paper, we describe a subset of lymphoid cells that is involved in innate type 2 immunity in the lungs. Airway exposure of naive BALB/c or C57BL/6J mice to IL-33 results in a rapid (<12 h) production of IL-5 and IL-13 and marked airway eosinophilia independently of adaptive immunity. In the lungs of nonsensitized naive mice, IL-33-responsive cells were identified that have a lymphoid morphology, lack lineage markers, highly express CD25, CD44, Thy1.2, ICOS, Sca-1, and IL-7Rα (i.e., Lin(-)CD25(+)CD44(hi) lymphoid cells), and require IL-7Rα for their development. Airway exposure of naive mice to a clinically relevant ubiquitous fungal allergen, Alternaria alternata, increases bronchoalveolar lavage levels of IL-33, followed by IL-5 and IL-13 production and airway eosinophilia without T or B cells. This innate type 2 response to the allergen is nearly abolished in mice deficient in IL-33R (i.e., ST2), and the Lin(-)CD25(+)CD44(hi) lymphoid cells in the lungs are required and sufficient to mediate the response. Thus, a subset of innate immune cells that responds to IL-33 and vigorously produces Th2-type cytokines is present in mouse lungs. These cells may provide a novel mechanism for type 2 immunity in the airways and induction of allergic airway diseases such as asthma.
authors.affiliation: Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Bartemes
authors.forename: Koji
authors.initials: K
authors.lastname: Iijima
authors.forename: Takao
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Gail M
authors.initials: GM
authors.lastname: Kephart
authors.forename: Andrew N
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
mesh_terms: D000485:Allergens / Q000276:immunology; D000528:Alternaria / Q000276:immunology; D000818:Animals; D019070:Cell Lineage; D018960:Hyaluronan Receptors; D007113:Immunity, Innate / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D011014:Pneumonia / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D018960:Hyaluronan Receptors; C506535:Il33 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000067596:Interleukin-33; D007378:Interleukins