Progranulin Inhibits Human T Lymphocyte Proliferation by Inducing the Formation of Regulatory T Lymphocytes

• Published in: Mediators of inflammation 2017-01, Vol.2017 (2017), p.1-9
• Main Authors: Kwack, Kyu Hwan, Lee, Hyeon-Woo
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Experiments; Flow cytometry; Health aspects; Humans; Intercellular Signaling Peptides and Proteins - pharmacology; Kinases; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lymphocytes; Membrane proteins; Proteins; Rodents; Signal transduction; Software; Standard deviation; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - metabolism; Transforming Growth Factor beta - metabolism; Tumor necrosis factor-TNF
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2017/7682083

We have examined the effect of progranulin (PGRN) on human T cell proliferation and its underlying mechanism. We show that PGRN inhibits the PHA-induced multiplication of T lymphocytes. It increases the number of iTregs when T lymphocytes are activated by PHA but does not do so in the absence of PHA. PGRN-mediated inhibition of T lymphocyte proliferation, as well as the induction of iTregs, was completely reversed by a TGF-β inhibitor or a Treg inhibitor. PGRN induced TGF-β secretion in the presence of PHA whereas it did not in the absence of PHA. Our findings indicate that PGRN suppresses T lymphocyte proliferation by enhancing the formation of iTregs from activated T lymphocytes in response to TGF-β.