In vitro differentiated human CD4+ T cells produce hepatocyte growth factor

• Published in: Frontiers in immunology Vol. 14; p. 1210836
• Main Authors: Ford, Shayne Lavondua, Buus, Terkild Brink, Nastasi, Claudia, Geisler, Carsten, Bonefeld, Charlotte Menné, Ødum, Niels, Woetmann, Anders
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 13.07.2023
• Subjects: c-Met; cytokine; growth factor; hepatocyte growth factor; HGF; Immunology; T cell; cytokine; growth factor; T cell; HGF; hepatocyte growth factor; c-Met; sequencing
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1210836

Differentiation of naive CD4 + T cells into effector T cells is a dynamic process in which the cells are polarized into T helper (Th) subsets. The subsets largely consist of four fundamental categories: Th1, Th2, Th17, and regulatory T cells. We show that human memory CD4 + T cells can produce hepatocyte growth factor (HGF), a pleiotropic cytokine which can affect several tissue types through signaling by its receptor, c-Met. In vitro differentiation of T cells into Th-like subsets revealed that HGF producing T cells increase under Th1 conditions. Enrichment of HGF producing cells was possible by targeting cells with surface CD30 expression, a marker discovered through single-cell RNA-sequencing. Furthermore, pharmacological inhibition of PI3K or mTOR was found to inhibit HGF mRNA and protein, while an Akt inhibitor was found to increase these levels. The findings suggest that HGF producing T cells could play a role in disease where Th1 are present.