Lilla Erdei, Beáta Szilvia Bolla, Renáta Bozó, Gábor Tax, Edit Urbán, Katalin Burián, Lajos Kemény, Kornélia Szabó
DOI: 10.2340/00015555-3707

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.

The control of cutaneous microbiota-induced immune activation in keratinocytes is key to the maintenance of epidermal homeostasis. Tumour necrosis factor alpha-induced protein 3, a regulator of nuclear factor kappa B signalling pathways, has important roles in these processes. It forms a negative regulatory feedback loop, controls the activity of toll-like receptor-induced signalling pathways, but is also regulated by different toll-like receptor ligands and by Cutibacterium acnes. The levels of tumour necrosis factor alpha-induced protein 3 greatly influence levels of bacterium-induced inflammatory mediator in keratinocytes. This study found elevated expression of tumour necrosis factor alpha-induced protein 3 mRNA in acne lesions. These finding suggest a general role of tumour necrosis factor alpha-induced protein 3, not only in the regulation of toll-like receptor-induced immune activation, but also in cutaneous immune homeostasis.

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