Transforming growth factor beta induces fibroblasts to express and release the immunomodulatory protein PD-L1 into extracellular vesicles
| Autor: | Edward B. Leof, Malay Choudhury, Mi-Yeon Jung, Jeong Han Kang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
T cell Biochemistry B7-H1 Antigen Extracellular matrix 03 medical and health sciences Extracellular Vesicles Mice 0302 clinical medicine Fibrosis Transforming Growth Factor beta PD-L1 Genetics medicine Animals Humans Fibroblast Molecular Biology biology Chemistry Cell migration Transforming growth factor beta 3T3 Cells Fibroblasts medicine.disease Cell biology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation biology.protein Wound healing 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(2) |
| ISSN: | 1530-6860 |
| Popis: | Transforming growth factor-beta (TGFβ) is an enigmatic protein with various roles in healthy tissue homeostasis/development as well as the development or progression of cancer, wound healing, fibrotic disorders, and immune modulation, to name a few. As TGFβ is causal to various fibroproliferative disorders featuring localized or systemic tissue/organ fibrosis as well as the activated stroma observed in various malignancies, characterizing the pathways and players mediating its action is fundamental. In the current study, we found that TGFβ induces the expression of the immunoinhibitory molecule Programed death-ligand 1 (PD-L1) in human and murine fibroblasts in a Smad2/3- and YAP/TAZ-dependent manner. Furthermore, PD-L1 knockdown decreased the TGFβ-dependent induction of extracellular matrix proteins, including collagen Iα1 (colIα1) and alpha-smooth muscle actin (α-SMA), and cell migration/wound healing. In addition to an endogenous role for PD-L1 in profibrotic TGFβ signaling, TGFβ stimulated-human lung fibroblast-derived PD-L1 into extracellular vesicles (EVs) capable of inhibiting T cell proliferation in response to T cell receptor stimulation and mediating fibroblast cell migration. These findings provide new insights and potential targets for a variety of fibrotic and malignant diseases. |
| Databáze: | OpenAIRE |
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