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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...

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Autores principales: De La Cruz Diaz, Jacinto S., Hirai, Toshiro, Anh-Thu Nguyen, Breanna, Zenke, Yukari, Yang, Yi, Li, Haiyue, Nishimura, Stephen, Kaplan, Daniel H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
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.
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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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