IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice.
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.
Wilson
Mark S
MS
Immunopathogenesis Section, Laboratory of Parasitic Diseases, and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
Elnekave
Eldad
E
Mentink-Kane
Margaret M
MM
Hodges
Marcus G
MG
Pesce
John T
JT
Ramalingam
Thirumalai R
TR
Thompson
Robert W
RW
Kamanaka
Masahito
M
Flavell
Richard A
RA
Keane-Myers
Andrea
A
Cheever
Allen W
AW
Wynn
Thomas A
TA
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*
D053663:Interleukin-13 Receptor alpha2 Subunit; D016753:Interleukin-10