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TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation
In the skin, Langerhans cells (LCs) require autocrine latent TGFβ that is transactivated by the integrins ανβ6 and ανβ8 expressed by keratinocytes (KCs) for long-term epidermal retention. Selective expression of a ligand-independent, constitutively active form of TGFβR1 inhibits LC migration during...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659779/ https://www.ncbi.nlm.nih.gov/pubmed/34909727 http://dx.doi.org/10.1016/j.xjidi.2021.100028 |
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author | De La Cruz Diaz, Jacinto S. Hirai, Toshiro Anh-Thu Nguyen, Breanna Zenke, Yukari Yang, Yi Li, Haiyue Nishimura, Stephen Kaplan, Daniel H. |
author_facet | De La Cruz Diaz, Jacinto S. Hirai, Toshiro Anh-Thu Nguyen, Breanna Zenke, Yukari Yang, Yi Li, Haiyue Nishimura, Stephen Kaplan, Daniel H. |
author_sort | De La Cruz Diaz, Jacinto S. |
collection | PubMed |
description | In the skin, Langerhans cells (LCs) require autocrine latent TGFβ that is transactivated by the integrins ανβ6 and ανβ8 expressed by keratinocytes (KCs) for long-term epidermal retention. Selective expression of a ligand-independent, constitutively active form of TGFβR1 inhibits LC migration during homeostasis and in response to UVB exposure. In this study, we found that LC migration in response to inflammatory stimuli was also inhibited by ligand-independent TGFβR1 signaling. Contrary to UVB stimulation, which reduced KC expression of ανβ6, in vitro and in vivo exposure to TNF-α or IL-1β increased ανβ6 transcript and protein expression by KCs. This resulted in increased KC-mediated transactivation of latent TGFβ. Expression of ανβ8 was largely unchanged. These findings show that ligand-independent TGFβR1 signaling in LCs can overcome inflammatory migration stimuli, but reduced KC-mediated transactivation of latent TGFβ by KCs may only drive LC migration during homeostasis and in response to UV stimulation. |
format | Online Article Text |
id | pubmed-8659779 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-86597792021-12-13 TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation De La Cruz Diaz, Jacinto S. Hirai, Toshiro Anh-Thu Nguyen, Breanna Zenke, Yukari Yang, Yi Li, Haiyue Nishimura, Stephen Kaplan, Daniel H. JID Innov Original Article In the skin, Langerhans cells (LCs) require autocrine latent TGFβ that is transactivated by the integrins ανβ6 and ανβ8 expressed by keratinocytes (KCs) for long-term epidermal retention. Selective expression of a ligand-independent, constitutively active form of TGFβR1 inhibits LC migration during homeostasis and in response to UVB exposure. In this study, we found that LC migration in response to inflammatory stimuli was also inhibited by ligand-independent TGFβR1 signaling. Contrary to UVB stimulation, which reduced KC expression of ανβ6, in vitro and in vivo exposure to TNF-α or IL-1β increased ανβ6 transcript and protein expression by KCs. This resulted in increased KC-mediated transactivation of latent TGFβ. Expression of ανβ8 was largely unchanged. These findings show that ligand-independent TGFβR1 signaling in LCs can overcome inflammatory migration stimuli, but reduced KC-mediated transactivation of latent TGFβ by KCs may only drive LC migration during homeostasis and in response to UV stimulation. Elsevier 2021-05-24 /pmc/articles/PMC8659779/ /pubmed/34909727 http://dx.doi.org/10.1016/j.xjidi.2021.100028 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article De La Cruz Diaz, Jacinto S. Hirai, Toshiro Anh-Thu Nguyen, Breanna Zenke, Yukari Yang, Yi Li, Haiyue Nishimura, Stephen Kaplan, Daniel H. TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation |
title | TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation |
title_full | TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation |
title_fullStr | TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation |
title_full_unstemmed | TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation |
title_short | TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation |
title_sort | tnf-α and il-1β do not induce langerhans cell migration by inhibiting tgfβ activation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659779/ https://www.ncbi.nlm.nih.gov/pubmed/34909727 http://dx.doi.org/10.1016/j.xjidi.2021.100028 |
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