title: Cooperation between IL-7 Receptor and Integrin α2β1 (CD49b) Drives Th17-Mediated Bone Loss.
abstract: Th17 cells are critical effectors in inflammation and tissue damage such as bone erosion, but the mechanisms regulating their activation in this process are not fully understood. In this study, we considered the cooperation between cytokine receptors and integrin pathways in Th17-osteoclast function. We found that human Th17 cells coexpress IL-7R and the collagen-binding integrin α2β1 (CD49b), and IL-7 increases their adhesion to collagen via α2β1 integrin. In addition, coengagement of the two receptors in human Th17 cells cooperatively enhanced their IL-17 production and their osteoclastogenic function. The functional cooperation between IL-7R and α2β1 integrin involves activation of the JAK/PI3K/AKT (protein kinase B) and MAPK/ERK pathways. We also showed that IL-7-induced bone loss in vivo is associated with Th17 cell expansion. Moreover, blockade of α2β1 integrin with a neutralizing mAb inhibited IL-7-induced bone loss and osteoclast numbers by reducing Th17 cell numbers in the bone marrow and reducing the production of IL-17 and the receptor activator of NF-κB ligand. Thus, the cooperation between IL-7R and α2β1 integrin can represent an important pathogenic pathway in Th17-osteoclast function associated with inflammatory diseases.
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Quebec City, Quebec G1V 4G2, Canada;
authors.forename: Mohammed-Amine
authors.initials: MA
authors.lastname: El Azreq
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Quebec City, Quebec G1V 4G2, Canada;
authors.forename: Claudie
authors.initials: C
authors.lastname: Arseneault
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Quebec City, Quebec G1V 4G2, Canada;
authors.forename: Marc
authors.initials: M
authors.lastname: Boisvert
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Quebec City, Quebec G1V 4G2, Canada;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pagé
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Quebec City, Quebec G1V 4G2, Canada;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Allaeys
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Quebec City, Quebec G1V 4G2, Canada; Département de Médecine, Faculté de Médecine de l'Université Laval, Quebec City, Quebec G1V 0A6, Canada; and.
authors.forename: Patrice E
authors.initials: PE
authors.lastname: Poubelle
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Quebec City, Quebec G1V 4G2, Canada; Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine de l'Université Laval, Quebec City, Quebec G1V 0A6, Canada.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Tessier
authors.affiliation: Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Quebec City, Quebec G1V 4G2, Canada; Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine de l'Université Laval, Quebec City, Quebec G1V 0A6, Canada fawzi.aoudjit@crchul.ulaval.ca.
authors.forename: Fawzi
authors.initials: F
authors.lastname: Aoudjit
mesh_terms: D001862:Bone Resorption / Q000209:etiology*; D002448:Cell Adhesion; D016764:Cell Polarity; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D038982:Integrin alpha2beta1 / Q000502:physiology*; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D020395:Receptors, Interleukin-7 / Q000502:physiology*; D058504:Th17 Cells / Q000502:physiology*
chemical_list: D038982:Integrin alpha2beta1; D020395:Receptors, Interleukin-7; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt