TY - JOUR T1 - Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD JF - Gut JO - Gut SP - 1072 LP - 1081 DO - 10.1136/gutjnl-2014-306947 VL - 64 IS - 7 AU - Thomas Ciucci AU - Lidia Ibáñez AU - Agathe Boucoiran AU - Eléonore Birgy-Barelli AU - Jérôme Pène AU - Grazia Abou-Ezzi AU - Nadia Arab AU - Matthieu Rouleau AU - Xavier Hébuterne AU - Hans Yssel AU - Claudine Blin-Wakkach AU - Abdelilah Wakkach Y1 - 2015/07/01 UR - http://gut.bmj.com/content/64/7/1072.abstract N2 - 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.Design CD4+ T cells were studied in IL10−/− mice and Rag1−/− mice adoptively transferred with naive CD4+CD45RBhigh 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. ER -