Susceptibility-associated genetic variation at IL12B enhances Th1 polarization in psoriasis.
Hum Mol Genet
; 22(9): 1807-15, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23376980
ABSTRACT
The IL12B gene encodes the common p40 subunit of IL-12 and IL-23, cytokines with key roles in Th1 and Th17 biology, respectively, and genetic variation in this region significantly influences risk of psoriasis. Here, we demonstrate that a psoriasis-associated risk haplotype at the IL12B locus leads to increased expression of IL12B by monocytes and correlated with increased serum levels of IL-12, IFN-γ and the IFN-γ induced chemokine, CXCL10. In contrast, serum IL-23 levels were decreased in risk carriers when compared with non-carriers. We further demonstrate that IL-12 is increased in psoriatic skin and that risk carriers manifest a skewing of the inflammatory network toward stronger IFN-γ responses. Taken together, our data demonstrate that the risk variant in IL12B associates with its increased expression and predisposes to stronger Th1 polarization through deviation of the local inflammatory environment toward increased IL-12/IFN-γ at the expense of IL-23/IL-17 responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Variação Genética
/
Células Th1
/
Predisposição Genética para Doença
/
Subunidade p40 da Interleucina-12
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Mol Genet
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos