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Transforming Growth Factor Beta Induces Fibroblasts to Express and Release the Immunomodulatory Protein PD‐L1 into Extracellular Vesicles
Author(s) -
Kang Jeonghan,
Jung MiYeon,
Leof Edward B
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.476.12
Subject(s) - microbiology and biotechnology , fibrosis , transforming growth factor , cancer research , tgf beta signaling pathway , immune system , transforming growth factor beta , biology , receptor , immunology , medicine , pathology , biochemistry
Transforming growth factor beta (TGF‐β) is an enigmatic protein with various roles in normal tissue homeostasis/development as well as the development and/or progression of cancer, wound healing, fibrotic disorders, and immune modulation, to name a few. As TGF‐β is causal to various fibroproliferative disorders featuring localized or systemic tissue/organ fibrosis as well as the activated stroma observed in numerous malignancies, characterizing the pathways and players mediating its action is fundamental. To that end, in the current study we found that (i) TGF‐β induces the expression of the immunoinhibitory molecule Programmed Death‐Ligand 1 (PD‐L1) in human and murine fibroblasts in a Smad2/3‐dependent manner; (ii) profibrotic TGF‐β signaling is dependent upon PD‐L1 expression; and (iii) following treatment with TGF‐β, human lung fibroblasts secrete PD‐L1 into extracellular vesicles (EVs) capable of inhibiting T‐cell proliferation in response to T cell receptor stimulation. These findings provide new insights and potential targets for a variety of fibrotic and/or malignant diseases. Support or Funding Information This work was supported by Public Health Service grants GM‐55816 and GM‐54200 from the National Institute of General Medical Sciences. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .