Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784794345128329216
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
work_keys_str_mv AT okunodaisuke twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT sakamotonoriho twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT akiyamayoshiko twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT tokitotakatomo twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT haraatsuko twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT kidotakashi twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT ishimotohiroshi twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT ishimatsuyuji twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT tagodmohammedso twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT okamuraharuki twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT tanakayoshimasa twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts
AT mukaehiroshi twodistinctmechanismsunderlyinggdtcellmediatedregulationofcollagentypeiinlungfibroblasts