Interleukin (IL)-12 family cytokines comprised of a heterodimer, including IL-12, IL-23, IL-27, and IL-35, play critical roles in multiple immune response such as psoriasis. A new cytokine IL-39 comprised of IL-23p19 and Epstein-Barr Virus-induced 3 (EBI3), was firstly reported in 2015. The mRNA of IL-23p19 and EBI3 has been detected respectively in keratinocytes stimulated with poly(I:C). In addition, IL-39 has been shown to mediate inflammation and expansion of neutrophils in lupus model mice. Clinically, an anti-interleukin-23p19 monoclonal antibody such as guselkumab has a good response to moderate-to-severe psoriasis in adult patients. IL-39 might be involved in the pathogenesis of psoriasis and guselkumab might bind to both IL-23 and IL-39. However, the association between IL-39 and psoriasis has not been reported yet.
To clarify the association, we here focused on normal human epidermal keratinocytes (NHEKs) and stimulated the cells with inflammatory cytokines related to psoriasis, such as tumor necrosis factor-α(TNF-α), IL-17A, IFN-γ, and those combination, and analysed the expressions of human p19, EBI3 with real-time PCR, and p19, EBI3, and IL-39 protein in NHEK culture media with ELISA.
We observed that the expressions of p19 and EBI3 were notable elevated especially with stimulating of three cytokines combination. In addition, p19 and EBI3 protein were detected in the supernatant under these stimulations. However, we have not detected the protein of IL-39, the heterodimer of p19 and EBI3, so far. These results suggest that there are some possibilities. Epidermal keratinocytes express p19. The p19 may form IL-39 with EBI3 at undetectable concentration, or form another unknown heterodimeric cytokine, or exist as monomer or homodimer.

The expression of p19 and EBI3 in epidermal keratinocytes under the stimulation with inflammatory cytokines