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. 2016 Oct;31(10):1899-1908.
doi: 10.1002/jbmr.2868. Epub 2016 Jun 30.

Inflammatory Osteoclasts Prime TNFα-Producing CD4+ T Cells and Express CX3 CR1

Lidia Ibáñez  1   2 , Grazia Abou-Ezzi  1   2 , Thomas Ciucci  1   2 , Vanessa Amiot  1   2 , Nourhène Belaïd  1   2 , Dorian Obino  3 , Anna Mansour  1   2 , Matthieu Rouleau  1   2 , Abdelilah Wakkach  1   2 , Claudine Blin-Wakkach  4   5
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Free article

Inflammatory Osteoclasts Prime TNFα-Producing CD4+ T Cells and Express CX3 CR1

Lidia Ibáñez et al. J Bone Miner Res. 2016 Oct.
Free article

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 CX3 CR1 as a marker of inflammatory osteoclasts and we demonstrated that the differentiation of CX3 CR1+ 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 CX3 CR1 as a novel dual target for antiresorptive and anti-inflammatory treatment in inflammatory chronic diseases. © 2016 American Society for Bone and Mineral Research.

Keywords: DENDRITIC CELLs; IBD; INFLAMMATION; OSTEOCLASTS; OSTEOIMMUNOLOGY; T CELLS.

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