Antagonistic Effects of IL-4 on IL-17A-Mediated Enhancement of Epidermal Tight Junction Function
by
Matthew G. Brewer 1
, Takeshi Yoshida 1, Fiona I. Kuo 1, Sade Fridy 1, Lisa A. Beck 1 and Anna De Benedetto 1,2,*
Matthew G. Brewer 1, Takeshi Yoshida 1, Fiona I. Kuo 1, Sade Fridy 1, Lisa A. Beck 1 and Anna De Benedetto 1,2,*
1
Department of Dermatology, University of Rochester Medical Center, Rochester, NY 14642, USA
2
Department of Dermatology, College of Medicine University of Florida, Gainesville, FL 32610, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(17), 4070; https://doi.org/10.3390/ijms20174070
Received: 2 August 2019 / Revised: 12 August 2019 / Accepted: 13 August 2019 / Published: 21 August 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease. AD is typically characterized by skewed T helper (Th) 2 inflammation, yet other inflammatory profiles (Th1, Th17, Th22) have been observed in human patients. How cytokines from these different Th subsets impact barrier function in this disease is not well understood. As such, we investigated the impact of the canonical Th17 cytokine, IL-17A, on barrier function and protein composition in primary human keratinocytes and human skin explants. These studies demonstrated that IL-17A enhanced tight junction formation and function in both systems, with a dependence on STAT3 signaling. Importantly, the Th2 cytokine, IL-4 inhibited the barrier-enhancing effect of IL-17A treatment. These observations propose that IL-17A helps to restore skin barrier function, but this action is antagonized by Th2 cytokines. This suggests that restoration of IL-17/IL-4 ratio in the skin of AD patients may improve barrier function and in so doing improve disease severity.
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Keywords:
atopic dermatitis; tight junctions; cytokines; claudin; STAT3
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MDPI and ACS Style
Brewer, M.G.; Yoshida, T.; Kuo, F.I.; Fridy, S.; Beck, L.A.; De Benedetto, A. Antagonistic Effects of IL-4 on IL-17A-Mediated Enhancement of Epidermal Tight Junction Function. Int. J. Mol. Sci. 2019, 20, 4070.
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