RhoH is a negative regulator of eosinophilopoiesis.

Stoeckle, Christina; Geering, Barbara; Yousefi, Shida; Rožman, Saša; Andina, Nicola; Benarafa, Charaf; Simon, Hans-Uwe (2016). RhoH is a negative regulator of eosinophilopoiesis. Cell death and differentiation, 23(12), pp. 1961-1972. Nature Publishing Group 10.1038/cdd.2016.73

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Yousefi, Shida; Benarafa, Charaf and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1350-9047

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Jana Berger

Date Deposited:

08 Mar 2017 11:02

Last Modified:

26 Mar 2019 13:39

Publisher DOI:

10.1038/cdd.2016.73

PubMed ID:

27740624

BORIS DOI:

10.7892/boris.92138

URI:

https://boris.unibe.ch/id/eprint/92138

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