Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice

Abstract Psoriasis (PS) is a chronic skin inflammation. Up to 30% of the patients with PS develop psoriatic arthritis (PsA), a condition characterized by inflammatory arthritis that affects joints or entheses. Although there is mounting evidence for a critical role of interleukin-23 (IL-23) signalin...

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Autores principales:	Lili Chen, Madhura Deshpande, Marcos Grisotto, Paola Smaldini, Roberto Garcia, Zhengxiang He, Percio S. Gulko, Sergio A. Lira, Glaucia C. Furtado
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d46e0aa1bb81478b9dd088bb5b12120a
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spelling	oai:doaj.org-article:d46e0aa1bb81478b9dd088bb5b12120a2021-12-02T14:59:13ZSkin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice10.1038/s41598-020-65269-62045-2322https://doaj.org/article/d46e0aa1bb81478b9dd088bb5b12120a2020-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-65269-6https://doaj.org/toc/2045-2322Abstract Psoriasis (PS) is a chronic skin inflammation. Up to 30% of the patients with PS develop psoriatic arthritis (PsA), a condition characterized by inflammatory arthritis that affects joints or entheses. Although there is mounting evidence for a critical role of interleukin-23 (IL-23) signaling in the pathogenesis of both PS and PsA, it remains unclear whether IL-23-induced skin inflammation drives joint disease. Here, we show that mice expressing increased levels of IL-23 in the skin (K23 mice) develop a PS-like disease that is characterized by acanthosis, parakeratosis, hyperkeratosis, and inflammatory infiltrates in the dermis. Skin disease preceded development of PsA, including enthesitis, dactylitis, and bone destruction. The development of enthesitis and dactylitis was not due to high circulating levels of IL-23, as transgenic animals and controls had similar levels of this cytokine in circulation. IL-22, a downstream cytokine of IL-23, was highly increased in the serum of K23 mice. Although IL-22 deficiency did not affect skin disease development, IL-22 deficiency aggravated the PsA-like disease in K23 mice. Our results demonstrate a central role for skin expressed IL-23 in the initiation of PS and on pathogenic processes leading to PsA.Lili ChenMadhura DeshpandeMarcos GrisottoPaola SmaldiniRoberto GarciaZhengxiang HePercio S. GulkoSergio A. LiraGlaucia C. FurtadoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lili Chen Madhura Deshpande Marcos Grisotto Paola Smaldini Roberto Garcia Zhengxiang He Percio S. Gulko Sergio A. Lira Glaucia C. Furtado Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice
description	Abstract Psoriasis (PS) is a chronic skin inflammation. Up to 30% of the patients with PS develop psoriatic arthritis (PsA), a condition characterized by inflammatory arthritis that affects joints or entheses. Although there is mounting evidence for a critical role of interleukin-23 (IL-23) signaling in the pathogenesis of both PS and PsA, it remains unclear whether IL-23-induced skin inflammation drives joint disease. Here, we show that mice expressing increased levels of IL-23 in the skin (K23 mice) develop a PS-like disease that is characterized by acanthosis, parakeratosis, hyperkeratosis, and inflammatory infiltrates in the dermis. Skin disease preceded development of PsA, including enthesitis, dactylitis, and bone destruction. The development of enthesitis and dactylitis was not due to high circulating levels of IL-23, as transgenic animals and controls had similar levels of this cytokine in circulation. IL-22, a downstream cytokine of IL-23, was highly increased in the serum of K23 mice. Although IL-22 deficiency did not affect skin disease development, IL-22 deficiency aggravated the PsA-like disease in K23 mice. Our results demonstrate a central role for skin expressed IL-23 in the initiation of PS and on pathogenic processes leading to PsA.
format	article
author	Lili Chen Madhura Deshpande Marcos Grisotto Paola Smaldini Roberto Garcia Zhengxiang He Percio S. Gulko Sergio A. Lira Glaucia C. Furtado
author_facet	Lili Chen Madhura Deshpande Marcos Grisotto Paola Smaldini Roberto Garcia Zhengxiang He Percio S. Gulko Sergio A. Lira Glaucia C. Furtado
author_sort	Lili Chen
title	Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice
title_short	Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice
title_full	Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice
title_fullStr	Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice
title_full_unstemmed	Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice
title_sort	skin expression of il-23 drives the development of psoriasis and psoriatic arthritis in mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d46e0aa1bb81478b9dd088bb5b12120a
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Skin expression of IL-23 drives the development of psoriasis and psoriatic arthritis in mice

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