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Publication : RhoH is a negative regulator of eosinophilopoiesis.

First Author  Stoeckle C Year  2016
Journal  Cell Death Differ Volume  23
Issue  12 Pages  1961-1972
PubMed ID  27740624 Mgi Jnum  J:258555
Mgi Id  MGI:6140432 Doi  10.1038/cdd.2016.73
Citation  Stoeckle C, et al. (2016) RhoH is a negative regulator of eosinophilopoiesis. Cell Death Differ 23(12):1961-1972
abstractText  Eosinophils are frequently elevated in pathological conditions and can cause tissue damage and disease exacerbation. The number of eosinophils in the blood is largely regulated by factors controlling their production in the bone marrow. While several exogenous factors, such as interleukin-5, have been described to promote eosinophil differentiation, comparatively little is known about eosinophil-intrinsic factors that control their de novo generation. Here, we report that the small atypical GTPase RhoH is induced during human eosinophil differentiation, highly expressed in mature blood eosinophils and further upregulated in patients suffering from a hypereosinophilic syndrome. Overexpression of RhoH increases, in a Rho-associated protein kinase-dependent manner, the expression of GATA-2, a transcription factor involved in regulating eosinophil differentiation. In RhoH(-/-) mice, we observed reduced GATA-2 expression as well as accelerated eosinophil differentiation both in vitro and in vivo. Conversely, RhoH overexpression in bone marrow progenitors reduces eosinophil development in mixed bone marrow chimeras. These results highlight a novel negative regulatory role for RhoH in eosinophil differentiation, most likely in consequence of altered GATA-2 levels.
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