Ecoeur, Florence, Weiss, Jessica and Guntermann, Christine (2020) Lack of evidence for expression and function of IL-39 in human immune cells. PLoS ONE, 2020 D (2020 D). pp. 1-16. ISSN 1932-6203

Abstract

Members of the IL-6/IL-12 cytokine family are critical regulators of innate and adaptive immunity and have emerged as key players controlling inflammatory and autoimmune disorders. This cytokine family is comprised of IL-12, IL-23, IL-27, and IL-35 and the members consists of distinct α- and β-cytokine subunits and form heterodimers. A new member belonging to this family, IL-39, was identified in the murine system and was shown to consist of the IL-23p19 and Epstein-Barr Virus-induced 3 (EBI3) subunits. Subsequently, it was shown that IL-39 was implicated in the immunopathogenesis of murine experimental lupus erythematosus. The existence of IL-39 in the human system has yet to be confirmed. Based on the clinical success of IL-23p19 neutralizing approaches in moderate-to-severe psoriasis, anti-IL-23p19 antibodies in the clinic may not only neutralize IL-23, but additionally IL-39, implying that IL-39 might also contribute to the pathogenesis of psoriasis. It is therefore pivotal to demonstrate IL-39 expression and to characterize its function in the human system. In this study, we provided evidence for the existence of secreted heterodimeric p19 and EBI3 assemblies from supernatants originating from p19 and EBI3 transfected HEK293FT cells. We attempted to detect IL-39 expression from stimulated B-cells, human keratinocytes and in vitro polarized macrophages. Whereas, the expression of p19 and EBI3 were elevated, we failed to detect the heterodimeric p19 and EBI3 protein complex. Functional assays were conducted with conditioned media containing IL-39 or with a chimeric human recombinant IL-39 Fc protein. Reported immune cells targeted by IL-39, such as neutrophils and PBMCs, did not respond to IL-39 stimulation and IL-39 failed to activate STAT3 in a reporter cell line. These results suggest that immune cell derived human IL-39 cytokine is too low to be detectable or that it does not exist and has no functional role in the human system.

Item Type:	Article
Keywords:	IL-39, B-cells, neutrophils, STAT3
Date Deposited:	16 Dec 2020 00:45
Last Modified:	16 Dec 2020 00:45
URI:	https://oak.novartis.com/id/eprint/42001