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Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts
Idiopathic pulmonary fibrosis is a chronic intractable lung disease, leading to respiratory failure and death. Although anti-fibrotic agents delay disease progression, they are not considered curative treatments, and alternative modalities have attracted attention. We examined the effect of human γδ...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496746/ https://www.ncbi.nlm.nih.gov/pubmed/36139391 http://dx.doi.org/10.3390/cells11182816 |
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author | Okuno, Daisuke Sakamoto, Noriho Akiyama, Yoshiko Tokito, Takatomo Hara, Atsuko Kido, Takashi Ishimoto, Hiroshi Ishimatsu, Yuji Tagod, Mohammed S. O. Okamura, Haruki Tanaka, Yoshimasa Mukae, Hiroshi |
author_facet | Okuno, Daisuke Sakamoto, Noriho Akiyama, Yoshiko Tokito, Takatomo Hara, Atsuko Kido, Takashi Ishimoto, Hiroshi Ishimatsu, Yuji Tagod, Mohammed S. O. Okamura, Haruki Tanaka, Yoshimasa Mukae, Hiroshi |
author_sort | Okuno, Daisuke |
collection | PubMed |
description | Idiopathic pulmonary fibrosis is a chronic intractable lung disease, leading to respiratory failure and death. Although anti-fibrotic agents delay disease progression, they are not considered curative treatments, and alternative modalities have attracted attention. We examined the effect of human γδ T cells on collagen type I in lung fibroblasts. Collagen type I was markedly reduced in a γδ T cell number-dependent manner following treatment with γδ T cells expanded with tetrakis-pivaloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2. Collagen type I levels remained unchanged on addition of γδ T cells to the culture system through a trans-well culture membrane, suggesting that cell–cell contact is essential for reducing its levels in lung fibroblasts. Re-stimulating γδ T cells with (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) reduced collagen type I levels without cell–cell contact, indicating the existence of HMBPP-induced soluble anti-fibrotic factors in γδ T cells. Adding anti-interferon-γ (IFN-γ)-neutralizing mAb restored collagen type I levels, demonstrating that human γδ T cell-derived IFN-γ reduces collagen type I levels. Conversely, interleukin-18 augmented γδ T cell-induced suppression of collagen type I. Therefore, human γδ T cells reduce collagen levels in lung fibroblasts via two distinct mechanisms; adoptive γδ T cell transfer is potentially a new therapeutic candidate. |
format | Online Article Text |
id | pubmed-9496746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94967462022-09-23 Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts Okuno, Daisuke Sakamoto, Noriho Akiyama, Yoshiko Tokito, Takatomo Hara, Atsuko Kido, Takashi Ishimoto, Hiroshi Ishimatsu, Yuji Tagod, Mohammed S. O. Okamura, Haruki Tanaka, Yoshimasa Mukae, Hiroshi Cells Article Idiopathic pulmonary fibrosis is a chronic intractable lung disease, leading to respiratory failure and death. Although anti-fibrotic agents delay disease progression, they are not considered curative treatments, and alternative modalities have attracted attention. We examined the effect of human γδ T cells on collagen type I in lung fibroblasts. Collagen type I was markedly reduced in a γδ T cell number-dependent manner following treatment with γδ T cells expanded with tetrakis-pivaloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2. Collagen type I levels remained unchanged on addition of γδ T cells to the culture system through a trans-well culture membrane, suggesting that cell–cell contact is essential for reducing its levels in lung fibroblasts. Re-stimulating γδ T cells with (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) reduced collagen type I levels without cell–cell contact, indicating the existence of HMBPP-induced soluble anti-fibrotic factors in γδ T cells. Adding anti-interferon-γ (IFN-γ)-neutralizing mAb restored collagen type I levels, demonstrating that human γδ T cell-derived IFN-γ reduces collagen type I levels. Conversely, interleukin-18 augmented γδ T cell-induced suppression of collagen type I. Therefore, human γδ T cells reduce collagen levels in lung fibroblasts via two distinct mechanisms; adoptive γδ T cell transfer is potentially a new therapeutic candidate. MDPI 2022-09-09 /pmc/articles/PMC9496746/ /pubmed/36139391 http://dx.doi.org/10.3390/cells11182816 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Okuno, Daisuke Sakamoto, Noriho Akiyama, Yoshiko Tokito, Takatomo Hara, Atsuko Kido, Takashi Ishimoto, Hiroshi Ishimatsu, Yuji Tagod, Mohammed S. O. Okamura, Haruki Tanaka, Yoshimasa Mukae, Hiroshi Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts |
title | Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts |
title_full | Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts |
title_fullStr | Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts |
title_full_unstemmed | Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts |
title_short | Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts |
title_sort | two distinct mechanisms underlying γδ t cell-mediated regulation of collagen type i in lung fibroblasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496746/ https://www.ncbi.nlm.nih.gov/pubmed/36139391 http://dx.doi.org/10.3390/cells11182816 |
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