Susceptibility-associated genetic variation at IL12B enhances Th1 polarization in psoriasis

Andrew Johnston, Xianying Xing, William R. Swindell, James Kochkodan, Mary Beth Riblett, Rajan P. Nair, Philip E. Stuart, Jun Ding, John J. Voorhees, James T. Elder, Johann E. Gudjonsson

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish (US)
Article numberddt034
Pages (from-to)1807-1815
Number of pages9
JournalHuman molecular genetics
Volume22
Issue number9
DOIs
StatePublished - May 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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