Cargando…

Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage

Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing, and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and...

Descripción completa

Detalles Bibliográficos
Autores principales: Rognoni, Emanuel, Goss, Georgina, Hiratsuka, Toru, Sipilä, Kalle H, Kirk, Thomas, Kober, Katharina I, Lui, Prudence PokWai, Tsang, Victoria SK, Hawkshaw, Nathan J, Pilkington, Suzanne M, Cho, Inchul, Ali, Niwa, Rhodes, Lesley E, Watt, Fiona M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747514/
https://www.ncbi.nlm.nih.gov/pubmed/34939928
http://dx.doi.org/10.7554/eLife.71052
_version_ 1784630851711008768
author Rognoni, Emanuel
Goss, Georgina
Hiratsuka, Toru
Sipilä, Kalle H
Kirk, Thomas
Kober, Katharina I
Lui, Prudence PokWai
Tsang, Victoria SK
Hawkshaw, Nathan J
Pilkington, Suzanne M
Cho, Inchul
Ali, Niwa
Rhodes, Lesley E
Watt, Fiona M
author_facet Rognoni, Emanuel
Goss, Georgina
Hiratsuka, Toru
Sipilä, Kalle H
Kirk, Thomas
Kober, Katharina I
Lui, Prudence PokWai
Tsang, Victoria SK
Hawkshaw, Nathan J
Pilkington, Suzanne M
Cho, Inchul
Ali, Niwa
Rhodes, Lesley E
Watt, Fiona M
author_sort Rognoni, Emanuel
collection PubMed
description Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing, and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin. Lineage tracing and in vivo live imaging revealed that repair following acute UVR is predominantly mediated by papillary fibroblast proliferation and fibroblast reorganisation occurs with minimal migration. In contrast, chronic UVR exposure led to a permanent loss of papillary fibroblasts, with expansion of fibroblast membrane protrusions partially compensating for the reduction in cell number. Although UVR strongly activated Wnt signalling in skin, stimulation of fibroblast proliferation by epidermal β-catenin stabilisation did not enhance papillary dermis repair. Acute UVR triggered an infiltrate of neutrophils and T cell subpopulations and increased pro-inflammatory prostaglandin signalling in skin. Depletion of CD4- and CD8-positive cells resulted in increased papillary fibroblast depletion, which correlated with an increase in DNA damage, pro-inflammatory prostaglandins, and reduction in fibroblast proliferation. Conversely, topical COX-2 inhibition prevented fibroblast depletion and neutrophil infiltration after UVR. We conclude that loss of papillary fibroblasts is primarily induced by a deregulated inflammatory response, with infiltrating T cells supporting fibroblast survival upon UVR-induced environmental stress.
format Online
Article
Text
id pubmed-8747514
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-87475142022-01-12 Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage Rognoni, Emanuel Goss, Georgina Hiratsuka, Toru Sipilä, Kalle H Kirk, Thomas Kober, Katharina I Lui, Prudence PokWai Tsang, Victoria SK Hawkshaw, Nathan J Pilkington, Suzanne M Cho, Inchul Ali, Niwa Rhodes, Lesley E Watt, Fiona M eLife Cell Biology Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing, and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin. Lineage tracing and in vivo live imaging revealed that repair following acute UVR is predominantly mediated by papillary fibroblast proliferation and fibroblast reorganisation occurs with minimal migration. In contrast, chronic UVR exposure led to a permanent loss of papillary fibroblasts, with expansion of fibroblast membrane protrusions partially compensating for the reduction in cell number. Although UVR strongly activated Wnt signalling in skin, stimulation of fibroblast proliferation by epidermal β-catenin stabilisation did not enhance papillary dermis repair. Acute UVR triggered an infiltrate of neutrophils and T cell subpopulations and increased pro-inflammatory prostaglandin signalling in skin. Depletion of CD4- and CD8-positive cells resulted in increased papillary fibroblast depletion, which correlated with an increase in DNA damage, pro-inflammatory prostaglandins, and reduction in fibroblast proliferation. Conversely, topical COX-2 inhibition prevented fibroblast depletion and neutrophil infiltration after UVR. We conclude that loss of papillary fibroblasts is primarily induced by a deregulated inflammatory response, with infiltrating T cells supporting fibroblast survival upon UVR-induced environmental stress. eLife Sciences Publications, Ltd 2021-12-23 /pmc/articles/PMC8747514/ /pubmed/34939928 http://dx.doi.org/10.7554/eLife.71052 Text en © 2021, Rognoni et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Rognoni, Emanuel
Goss, Georgina
Hiratsuka, Toru
Sipilä, Kalle H
Kirk, Thomas
Kober, Katharina I
Lui, Prudence PokWai
Tsang, Victoria SK
Hawkshaw, Nathan J
Pilkington, Suzanne M
Cho, Inchul
Ali, Niwa
Rhodes, Lesley E
Watt, Fiona M
Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage
title Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage
title_full Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage
title_fullStr Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage
title_full_unstemmed Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage
title_short Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage
title_sort role of distinct fibroblast lineages and immune cells in dermal repair following uv radiation-induced tissue damage
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747514/
https://www.ncbi.nlm.nih.gov/pubmed/34939928
http://dx.doi.org/10.7554/eLife.71052
work_keys_str_mv AT rognoniemanuel roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT gossgeorgina roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT hiratsukatoru roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT sipilakalleh roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT kirkthomas roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT koberkatharinai roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT luiprudencepokwai roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT tsangvictoriask roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT hawkshawnathanj roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT pilkingtonsuzannem roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT choinchul roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT aliniwa roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT rhodeslesleye roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage
AT wattfionam roleofdistinctfibroblastlineagesandimmunecellsindermalrepairfollowinguvradiationinducedtissuedamage