Tumour Necrosis Factor Alpha-induced Protein 3 Negatively Regulates Cutibacterium acnes-induced Innate Immune Events in Epidermal Keratinocytes

Lilla Erdei; Beáta Szilvia Bolla; Renáta Bozó; Gábor Tax; Edit Urbán; Katalin Burián; Lajos Kemény; Kornélia Szabó

doi:10.2340/00015555-3707

Authors

Lilla Erdei
Beáta Szilvia Bolla
Renáta Bozó
Gábor Tax
Edit Urbán
Katalin Burián
Lajos Kemény
Kornélia Szabó Department of Dermatology and Allergology, University of Szeged, HU-6720 Szeged, Hungary

DOI:

https://doi.org/10.2340/00015555-3707

Keywords:

TNFAIP3, microbiota, Cutibacterium acnes, acne vulgaris, innate immunity

Abstract

Human epidermal keratinocytes sense the presence of human skin microbiota through pathogen recognition receptors, such as toll-like receptors, and induce innate immune and inflammatory events. In healthy epidermis there is an absence of inflammation despite the continuous presence of cutaneous microbes, which is evidence of an effective immune regulatory mechanism. The aim of this study was to investigate tumour necrosis factor alpha-induced protein 3 (TNFAIP3), a negative regulator of toll-like receptor and nuclear factor kappa B signalling pathways, and its role in these regulatory events. A broad spectrum of toll-like receptor ligands induced TNFAIP3 expression, as did live Cutibacterium acnes, which is involved in the pathogenesis of acne. Changes in bacterium-induced, dose-dependent TNFAIP3 expression were Jun kinase- and nuclear factor kappa B-dependent, and resulted in altered cytokine and chemokine levels in in vitro cultured human keratinocytes. In acne lesions, TNFAIP3 mRNA expression was elevated compared with non-lesional skin samples from the same individuals. These results suggest that TNFAIP3 may have a general role in fine regulation of microbiota-induced cutaneous immune homeostasis.

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