title: RhoH is a negative regulator of eosinophilopoiesis.
abstract: 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.
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Christina
authors.identifier: 0000-0001-8424-3365
authors.initials: C
authors.lastname: Stoeckle
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Barbara
authors.identifier: 0000-0001-7207-5819
authors.initials: B
authors.lastname: Geering
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Shida
authors.identifier: 0000-0002-9855-4305
authors.initials: S
authors.lastname: Yousefi
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Saša
authors.initials: S
authors.lastname: Rožman
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Andina
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Charaf
authors.identifier: 0000-0002-2049-7769
authors.initials: C
authors.lastname: Benarafa
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002452:Cell Count; D002453:Cell Cycle; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D002678:Chimera; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D015848:Interleukin-5 / Q000378:metabolism; D008136:Longevity; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D053649:Receptors, Interleukin-5 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D050989:GATA2 Transcription Factor; D015848:Interleukin-5; D053649:Receptors, Interleukin-5; C447841:RhoH protein, human; C496930:RhoH protein, mouse; D014157:Transcription Factors; D020741:rho GTP-Binding Proteins