1. Academic Validation
  2. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis

Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis

  • J Invest Dermatol. 2011 Dec;131(12):2428-37. doi: 10.1038/jid.2011.234.
Yijun Carrier 1 Hak-Ling Ma Hilda E Ramon Lee Napierata Clayton Small Margot O'Toole Deborah A Young Lynette A Fouser Cheryl Nickerson-Nutter Mary Collins Kyri Dunussi-Joannopoulos Quintus G Medley
Affiliations

Affiliation

  • 1 Inflammation and Immunology, BioTherapeutic Research, Pfizer, Cambridge, Massachusetts 02140, USA.
Abstract

Accumulating evidence indicates that IL-1 family members and Th17 cytokines have a pathogenic role in psoriasis. We investigated the regulatory interactions of the IL-1-like IL-36 cytokine family and the Th17 cytokines in the context of skin inflammation. We observed increased gene expression of all three IL-36 cytokines in a Th17-dominant psoriasis-like animal model. The induction was downregulated by neutralizing IL-22. Expression of the IL-36s was also induced in cultured primary human keratinocytes (KC) by IL-17A and tumor necrosis factor (TNF)-α, and IL-22 synergized with IL-17A and TNF-α. Furthermore, the IL-36s directly induced their own expression and the production of proinflammatory mediators (TNF-α, IL-6, IL-8) in KC. These functions were markedly enhanced with the addition of IL-17A or TNF-α to the cultures. Similarly, IL-36α and IL-36β augmented IL-17A-mediated induction of Antibacterial peptides. Finally, we show that the increased gene expression of IL-36 correlated with Th17 cytokines in the lesions of psoriatic patients. Our results indicate that the IL-36 cytokines are not only regulated by Th17 cytokines, but that they themselves can regulate the expression and enhance the function of Th17 cytokines. We propose that a feedback loop between the IL-36 and Th17 cytokines is involved in driving cytokine expression in psoriatic tissues.

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