title: IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice.
abstract: Development of persistent Th2 responses in asthma and chronic helminth infections are a major health concern. IL-10 has been identified as a critical regulator of Th2 immunity, but mechanisms for controlling Th2 effector function remain unclear. IL-10 also has paradoxical effects on Th2-associated pathology, with IL-10 deficiency resulting in increased Th2-driven inflammation but also reduced airway hyperreactivity (AHR), mucus hypersecretion, and fibrosis. We demonstrate that increased IL-13 receptor alpha 2 (IL-13Ralpha2) expression is responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10(-/-) mice. Using models of allergic asthma and chronic helminth infection, we demonstrate that IL-10 and IL-13Ralpha2 coordinately suppress Th2-mediated inflammation and pathology, respectively. Although IL-10 was identified as the dominant antiinflammatory mediator, studies with double IL-10/IL-13Ralpha2-deficient mice illustrate an indispensable role for IL-13Ralpha2 in the suppression of AHR, mucus production, and fibrosis. Thus, IL-10 and IL-13Ralpha2 are both required to control chronic Th2-driven pathological responses.
authors: Immunopathogenesis Section, Laboratory of Parasitic Diseases, and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
authors: Mark S
authors: MS
authors: Wilson
authors: Eldad
authors: E
authors: Elnekave
authors: Margaret M
authors: MM
authors: Mentink-Kane
authors: Marcus G
authors: MG
authors: Hodges
authors: John T
authors: JT
authors: Pesce
authors: Thirumalai R
authors: TR
authors: Ramalingam
authors: Robert W
authors: RW
authors: Thompson
authors: Masahito
authors: M
authors: Kamanaka
authors: Richard A
authors: RA
authors: Flavell
authors: Andrea
authors: A
authors: Keane-Myers
authors: Allen W
authors: AW
authors: Cheever
authors: Thomas A
authors: TA
authors: Wynn
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001991:Bronchitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005355:Fibrosis; D006099:Granuloma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009093:Mucus / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D053663:Interleukin-13 Receptor alpha2 Subunit; D016753:Interleukin-10