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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...

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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
Descripción
Sumario: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.