RGD Reference Report - Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. - Rat Genome Database

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Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma.

Authors: Lajoie, S  Lewkowich, IP  Suzuki, Y  Clark, JR  Sproles, AA  Dienger, K  Budelsky, AL  Wills-Karp, M 
Citation: Lajoie S, etal., Nat Immunol. 2010 Oct;11(10):928-35. Epub 2010 Aug 29.
RGD ID: 5129681
Pubmed: PMID:20802484   (View Abstract at PubMed)
PMCID: PMC2943538   (View Article at PubMed Central)
DOI: DOI:10.1038/ni.1926   (Journal Full-text)

Severe asthma is associated with the production of interleukin 17A (IL-17A). The exact role of IL-17A in severe asthma and the factors that drive its production are unknown. Here we demonstrate that IL-17A mediated severe airway hyperresponsiveness (AHR) in susceptible strains of mice by enhancing IL-13-driven responses. Mechanistically, we demonstrate that IL-17A and AHR were regulated by allergen-driven production of anaphylatoxins, as mouse strains deficient in complement factor 5 (C5) or the complement receptor C5aR mounted robust IL-17A responses, whereas mice deficient in C3aR had fewer IL-17-producing helper T cells (T(H)17 cells) and less AHR after allergen challenge. The opposing effects of C3a and C5a were mediated through their reciprocal regulation of IL-23 production. These data demonstrate a critical role for complement-mediated regulation of the IL-23-T(H)17 axis in severe asthma.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
C3Ratasthma  ISOC3 (Mus musculus)protein:increased expression:respiratory system fluid/secretionRGD 
C3Humanasthma  ISOC3 (Mus musculus)protein:increased expression:respiratory system fluid/secretionRGD 
C3Mouseasthma  IEP protein:increased expression:respiratory system fluid/secretionRGD 
C3AR1Humanasthma  ISOC3ar1 (Mus musculus) RGD 
C3ar1Ratasthma  ISOC3ar1 (Mus musculus) RGD 
C3ar1Mouseasthma  IMP  RGD 
C5Ratasthma  ISOHc (Mus musculus) RGD 
C5Humanasthma  ISOHc (Mus musculus) RGD 
C5AR1Humanasthma  ISOC5ar1 (Mus musculus) RGD 
C5ar1Ratasthma  ISOC5ar1 (Mus musculus) RGD 
C5ar1Mouseasthma  IMP  RGD 
HcMouseasthma  IAGP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
C3  (complement C3)
C3ar1  (complement C3a receptor 1)
C5  (complement C5)
C5ar1  (complement C5a receptor 1)

Genes (Mus musculus)
C3  (complement component 3)
C3ar1  (complement component 3a receptor 1)
C5ar1  (complement component 5a receptor 1)
Hc  (hemolytic complement)

Genes (Homo sapiens)
C3  (complement C3)
C3AR1  (complement C3a receptor 1)
C5  (complement C5)
C5AR1  (complement C5a receptor 1)


Additional Information