title: Inflammatory Osteoclasts Prime TNFα-Producing CD4+T Cells and Express CX3CR1.
abstract: Bone destruction is a hallmark of chronic rheumatic diseases. Although the role of osteoclasts in bone loss is clearly established, their implication in the inflammatory response has not been investigated despite their monocytic origin. Moreover, specific markers are lacking to characterize osteoclasts generated in inflammatory conditions. Here, we have explored the phenotype of inflammatory osteoclasts and their effect on CD4+T cell responses in the context of bone destruction associated with inflammatory bowel disease. We used the well-characterized model of colitis induced by transfer of naive CD4+T cells into Rag1-/-mice, which is associated with severe bone destruction. We set up a novel procedure to sort pure osteoclasts generated in vitro to analyze their phenotype and specific immune responses by FACS and qPCR. We demonstrated that osteoclasts generated from colitic mice induced the emergence of TNFα-producing CD4+T cells, whereas those generated from healthy mice induced CD4+FoxP3+regulatory T cells, in an antigen-dependent manner. This difference is related to the osteoclast origin from monocytes or dendritic cells, to their cytokine expression pattern, and their environment. We identified CX3CR1 as a marker of inflammatory osteoclasts and we demonstrated that the differentiation of CX3CR1+osteoclasts is controlled by IL-17 in vitro. This work is the first demonstration that, in addition to participating to bone destruction, osteoclasts also induce immunogenic CD4+T cell responses upon inflammation. They highlight CX3CR1 as a novel dual target for antiresorptive and anti-inflammatory treatment in inflammatory chronic diseases. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France.|Université Nice Sophia Antipolis, Nice, France.
authors.forename: Lidia
authors.initials: L
authors.lastname: Ibáñez
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France.|Université Nice Sophia Antipolis, Nice, France.
authors.forename: Grazia
authors.initials: G
authors.lastname: Abou-Ezzi
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France.|Université Nice Sophia Antipolis, Nice, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ciucci
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France.|Université Nice Sophia Antipolis, Nice, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Amiot
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France.|Université Nice Sophia Antipolis, Nice, France.
authors.forename: Nourhène
authors.initials: N
authors.lastname: Belaïd
authors.affiliation: INSERM-U932 Immunité et Cancer, Institut Curie, Paris Sciences et Lettres Research University, Paris, France.
authors.forename: Dorian
authors.initials: D
authors.lastname: Obino
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France.|Université Nice Sophia Antipolis, Nice, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Mansour
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France.|Université Nice Sophia Antipolis, Nice, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rouleau
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France.|Université Nice Sophia Antipolis, Nice, France.
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Wakkach
authors.affiliation: CNRS, LP2M, UMR7370, Faculté de Médecine, Nice, France. blin@unice.fr.|Université Nice Sophia Antipolis, Nice, France. blin@unice.fr.
authors.forename: Claudine
authors.initials: C
authors.lastname: Blin-Wakkach
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: DENDRITIC CELLs; IBD; INFLAMMATION; OSTEOCLASTS; OSTEOIMMUNOLOGY; T CELLS