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

Erdei, Lilla and Bolla, Beáta Szilvia and Bozó, Renáta and Tax, Gábor and Urbán, Edit and Burián, Katalin and Kemény, Lajos and Szabó, Kornélia (2021) Tumour Necrosis Factor Alpha-induced Protein 3 Negatively Regulates Cutibacterium acnes-induced Innate Immune Events in Epidermal Keratinocytes. ACTA DERMATO-VENEREOLOGICA, 101 (1). ISSN 0001-5555 (print); 1651-2057 (online)

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Abstract

Human epidermal keratinocytes sense the presence of human skin microbiota through pathogen recogni�tion 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 mecha�nism. 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 cul�tured 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

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