title: Pulmonary innate lymphoid cells are major producers of IL-5 and IL-13 in murine models of allergic asthma.
abstract: Allergic asthma is characterized by chronic airway inflammation and hyperreactivity and is thought to be mediated by an adaptive T helper-2 (Th2) cell-type immune response. Here, we demonstrate that type 2 pulmonary innate lymphoid cells (ILC2s) significantly contribute to production of the key cytokines IL-5 and IL-13 in experimental asthma. In naive mice, lineage-marker negative ILC2s expressing IL-7Rα, CD25, Sca-1, and T1/ST2(IL-33R) were present in lungs and mediastinal lymph nodes (MedLNs), but not in broncho-alveolar lavage (BAL) fluid. Upon intranasal administration of IL-25 or IL-33, an asthma phenotype was induced, whereby ILC2s accumulated in lungs, MedLNs, and BAL fluid. After IL-25 and IL-33 administration, ILC2s constituted ∼50 and ∼80% of IL-5(+) /IL-13(+) cells in lung and BAL, respectively. Also in house dust mite-induced or ovalbumin-induced allergic asthma, the ILC2 population in lung and BAL fluid increased significantly in size and ILC2s were a major source of IL-5 or IL-13. Particularly in OVA-induced asthma, the contribution of ILC2s to the total population of intracellular IL-5(+) and IL-13(+) cells in the lung was in the same range as found for Th2 cells. We conclude that both ILC2s and Th2 cells produce large amounts of IL-5 and IL-13 that contribute to allergic airway inflammation.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Roel G J
authors.initials: RG
authors.lastname: Klein Wolterink
authors.forename: Alex
authors.initials: A
authors.lastname: Kleinjan
authors.forename: Menno
authors.initials: M
authors.lastname: van Nimwegen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bergen
authors.forename: Marjolein
authors.initials: M
authors.lastname: de Bruijn
authors.forename: Yelvi
authors.initials: Y
authors.lastname: Levani
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D007113:Immunity, Innate; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000096:biosynthesis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000096:biosynthesis*; D007378:Interleukins / Q000008:administration & dosage; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D039981:Pyroglyphidae / Q000276:immunology; D018123:Receptors, Interleukin / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000950:Antigens, Ly; C486189:Il1rl1 protein, mouse; C508018:Il2ra protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D053645:Interleukin-2 Receptor alpha Subunit; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C442281:Mydgf protein, mouse; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain