title: The hepatocyte growth factor (HGF)-MET receptor tyrosine kinase signaling pathway: Diverse roles in modulating immune cell functions.
abstract: Hepatocyte growth factor (HGF) signaling via the MET receptor is essential for embryonic development and tissue repair. On the other hand, deregulated MET signaling promotes tumor progression in diverse types of cancers. Even though oncogenic MET signaling remains the major research focus, the HGF-MET axis has also been implicated in diverse aspects of immune cell development and functions. In the presence of other hematopoietic growth factors, HGF promotes the development of erythroid, myeloid and lymphoid lineage cells and thrombocytes. In monocytes and macrophages responding to inflammatory stimuli, induction of autocrine HGF-MET signaling can contribute to tissue repair via stimulating anti-inflammatory cytokine production. HGF-MET signaling can also modulate adaptive immune response by facilitating the migration of Langerhans cells and dendritic cells to draining lymph nodes. However, MET signaling has also been shown to induce tolerogenic dendritic cells in mouse models of graft-versus-host disease and experimental autoimmune encephalomyelitis. HGF-MET axis is also implicated in promoting thymopoiesis and the survival and migration of B lymphocytes. Recent studies have shown that MET signaling induces cardiotropism in activated T lymphocytes. Further understanding of the HGF-MET axis in the immune system would allow its therapeutic manipulation to improve immune cell reconstitution, restore immune homeostasis and to treat immuno-inflammatory diseases.
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke and CR-CHUS, Sherbrooke, Québec J1H 5N4, Canada. Electronic address: Subburaj.Ilangumaran@Usherbrooke.ca.
authors.forename: Subburaj
authors.initials: S
authors.lastname: Ilangumaran
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke and CR-CHUS, Sherbrooke, Québec J1H 5N4, Canada.
authors.forename: Alberto
authors.initials: A
authors.lastname: Villalobos-Hernandez
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke and CR-CHUS, Sherbrooke, Québec J1H 5N4, Canada.
authors.forename: Diwakar
authors.initials: D
authors.lastname: Bobbala
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke and CR-CHUS, Sherbrooke, Québec J1H 5N4, Canada.
authors.forename: Sheela
authors.initials: S
authors.lastname: Ramanathan
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D017228:Hepatocyte Growth Factor / Q000276:immunology*; D006801:Humans; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: B lymphocyte; Dendritic cell; HGF; Hematopoiesis; MET; Macrophage; Neutrophils; T lymphocyte