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. 2019 Jun;68(6):423-426.
doi: 10.1007/s00011-019-01235-x. Epub 2019 Apr 13.

The IL-23p19/EBI3 heterodimeric cytokine termed IL-39 remains a theoretical cytokine in man

Charlie Bridgewood  1 , Adewonuola Alase  2 , Abdulla Watad  2   3   4 , Miriam Wittmann  2   5 , Richard Cuthbert  2 , Dennis McGonagle  2   5
Affiliations

The IL-23p19/EBI3 heterodimeric cytokine termed IL-39 remains a theoretical cytokine in man

Charlie Bridgewood et al. Inflamm Res. 2019 Jun.

Erratum in

Abstract

Objective: The heterodimeric IL-12 family member cytokines including, IL-12, IL-23, IL-27, and IL-35 and have multiple roles in regulating innate and adaptive immunity with crucial functions in inflammatory disorders such as psoriasis. Chain pairing promiscuity is a feature of the IL-12 family. Recently, based on murine data, a new family member, IL-39, was proposed, consisting of IL23p19 (shared with IL-23) and EBI3 (shared with IL-27 and IL-35). IL-39 has subsequently been implicated in experimental murine lupus. Given the success of IL-23p19 therapeutic targeting in diseases including psoriasis, it is of great interest to confirm the presence of IL-39 in man. Human IL-39 is yet to be either detected or expressed, which has halted research in this area.

Methods: Using a disulphide-linked human chimera protein composing of IL-23p19 and EBI3 human chains, we stimulated human leukocytes, and analysed cytokine secretion and STAT3 phosphorylation.

Results and conclusion: We report that this cytokine shows no activity in human cells. IL-39 chimera protein failed to induce either IL-6, IL-8, TNF, or IL-17A from leukocytes or STAT3 phosphorylation and thus, remains a 'theoretical cytokine' in humans.

Keywords: Cytokine; IL-23; IL-39; Lupus; Psoriasis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
IL-39 shows no activity in human leukocytes. Human leukocytes were stimulated with IL-39 and or LPS, and secreted concentration of TNF, IL-6, and IL-8 was determined by ELISA (a, c and d). Leukocytes were stimulated with IL-39, with and without anti-CD3/CD28, and secreted concentration of IL-17 was determined by ELISA (b) (n = 4). Leukocytes were stimulated with IL-39 (100 ng/ml) or IL-6 (20 ng/ml) for 15 min and subsequently probed for phospho STAT3 or GAPDH using western blot method (e). Cells were stimulated as before, and subsequently intracellularly stained for phospho-STAT3, and signal measured using flow cytometry (f). a–d Significance reported between treatments and unstimulated (unless stated). Paired t-test
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