The function of eosinophils in bone remodelling

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Bone homeostasis is essentially controlled by the immune system. While the influence of cells and mediators of the adaptive immune system such as T cells and antibodies on bone has been well characterized, much less is known about the role of innate immune cells in controlling bone homeostasis. Surprisingly, among innate immune cells the role eosinophils seems particularly interesting. Apart from their role in host defence against parasites eosinophils are increasingly appreciated for their role in controlling tissue homeostasis. For instance, eosinophils control fat and temperature homeostasis by promoting the generation of beige fat. Furthermore, we and others have demonstrated that eosinophils are involved in the resolution of chronic inflammation such as arthritis by promoting the differentiation of anti-inflammatory macrophages. Hence, eosinophils hold interesting functional aspects that predispose them to play an active role in controlling bone homeostasis, especially by affecting the differentiation of osteoclasts. Preliminary data using genetically engineered mouse models support this concept and show that absence of eosinophils leads to exacerbated bone loss, while an increase in eosinophil numbers results in increased bone mass. We speculate that this bone protective effect of eosinophils is essentially based on their cytokines production pattern, which includes IL-4- a well-known negative regulator of osteoclastogenesis. Hence, the aim of this application is: (1) to characterize the bone phenotype and osteoclast differentiation in mice lacking eosinophils (delta dblGATA mice) and in mice with hyper eosinophilia (IL-5tg mice); (2) to analyse the importance of eosinophils in different models of pathological bone loss induced by immune activation, ageing and menopause; 3) to decipher the molecular mechanism how eosinophils regulate osteoclast differentiation; and (4) to translate our finding to humans by determining the effects of eosinophils on osteoclasts in the human system. In summary, these experiments will delineate the role of eosinophils in bone homeostasis.