title: Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD.
abstract: OBJECTIVE
  Under both physiological and pathological conditions, bone volume is determined by the rate of bone formation by osteoblasts and bone resorption by osteoclasts. Excessive bone loss is a common complication of human IBD whose mechanisms are not yet completely understood. Despite the role of activated CD4(+) T cells in inflammatory bone loss, the nature of the T cell subsets involved in this process in vivo remains unknown. The aim of the present study was to identify the CD4(+) T cell subsets involved in the process of osteoclastogenesis in vivo, as well as their mechanism of action.
  
  
  METHODS
  CD4(+) T cells were studied in IL10-/- mice and Rag1-/- mice adoptively transferred with naive CD4(+)CD45RB(high) T cells, representing two well-characterised animal models of IBD and in patients with Crohn's disease. They were phenotypically and functionally characterised by flow cytometric and gene expression analysis, as well as in in vitro cocultures with osteoclast precursors.
  
  
  RESULTS
  In mice, we identified bone marrow (BM) CD4(+) T cells producing interleukin (IL)-17 and tumour necrosis factor (TNF)-α as an osteoclastogenic T cell subset referred to as Th17 TNF-α(+) cells. During chronic inflammation, these cells migrate to the BM where they survive in an IL-7-dependent manner and where they promote the recruitment of inflammatory monocytes, the main osteoclast progenitors. A population equivalent to the Th17 TNF-α(+) cells was also detected in patients with Crohn's disease.
  
  
  CONCLUSIONS
  Our results highlight the osteoclastogenic function of the Th17 TNF-α(+) cells that contribute to bone loss in vivo in IBD.
authors.affiliation: CNRS, UMR 7370, LP2M, Faculté de médecine, 28 avenue de Valombrose, Nice, France Université Nice Sophia Antipolis, parc Valrose, Nice, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ciucci
authors.affiliation: CNRS, UMR 7370, LP2M, Faculté de médecine, 28 avenue de Valombrose, Nice, France Université Nice Sophia Antipolis, parc Valrose, Nice, France.
authors.forename: Lidia
authors.initials: L
authors.lastname: Ibáñez
authors.affiliation: CNRS, UMR 7370, LP2M, Faculté de médecine, 28 avenue de Valombrose, Nice, France Université Nice Sophia Antipolis, parc Valrose, Nice, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Boucoiran
authors.affiliation: CNRS, UMR 7370, LP2M, Faculté de médecine, 28 avenue de Valombrose, Nice, France Université Nice Sophia Antipolis, parc Valrose, Nice, France.
authors.forename: Eléonore
authors.initials: E
authors.lastname: Birgy-Barelli
authors.affiliation: Inserm, U844, Hôpital saint Eloi, Montpellier, France Université Montpellier 1, 5 bd Henri IV 34967, Montpellier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Pène
authors.affiliation: CNRS, UMR 7370, LP2M, Faculté de médecine, 28 avenue de Valombrose, Nice, France Université Nice Sophia Antipolis, parc Valrose, Nice, France.
authors.forename: Grazia
authors.initials: G
authors.lastname: Abou-Ezzi
authors.affiliation: Centre Hospitalier Universitaire de Nice, Hôpital de l'Archet, service de gastro-entérologie et nutrition, Nice, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Arab
authors.affiliation: CNRS, UMR 7370, LP2M, Faculté de médecine, 28 avenue de Valombrose, Nice, France Université Nice Sophia Antipolis, parc Valrose, Nice, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rouleau
authors.affiliation: Université Nice Sophia Antipolis, parc Valrose, Nice, France Centre Hospitalier Universitaire de Nice, Hôpital de l'Archet, service de gastro-entérologie et nutrition, Nice, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Hébuterne
authors.affiliation: Inserm, U844, Hôpital saint Eloi, Montpellier, France Université Montpellier 1, 5 bd Henri IV 34967, Montpellier, France.
authors.forename: Hans
authors.initials: H
authors.lastname: Yssel
authors.affiliation: CNRS, UMR 7370, LP2M, Faculté de médecine, 28 avenue de Valombrose, Nice, France Université Nice Sophia Antipolis, parc Valrose, Nice, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Blin-Wakkach
authors.affiliation: CNRS, UMR 7370, LP2M, Faculté de médecine, 28 avenue de Valombrose, Nice, France Université Nice Sophia Antipolis, parc Valrose, Nice, France.
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Wakkach
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D000818:Animals; D001847:Bone Diseases / Q000276:immunology / Q000503:physiopathology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D003424:Crohn Disease / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000503:physiopathology*; D015851:Interleukin-7 / Q000502:physiology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000276:immunology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D058504:Th17 Cells / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology
chemical_list: D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha
keywords: BONE MINERAL DENSITY; IBD; IMMUNOLOGY; T LYMPHOCYTES