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Cited by 24Eosinophilic Disorders and SyndromesAsthma and respiratory diseasesIL-33, ST2, and ILC Pathways

RhoH is a negative regulator of eosinophilopoiesis

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Stoeckle, Christina, Geering, Barbara, Yousefi, Shida, Rožman, Saša, Andina, Nicola, Benarafa, Charaf, Simon, Hans-Uwe·2016·Cell Death & Differentiation
DOI 10.1038/cdd.2016.73PMC PMC5136485
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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.

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Cited by

Sorted by citations

Authors
Stoeckle, C., Geering, B., Yousefi, S., Rožman, S., Andina, N., Benarafa, C., & Simon, H.-U.
Affiliations
  • University of Bern (CH)
  • F. Hoffmann-La Roche AG (CH)
Corresponding author
Simon, Hans-Uwe
ORCID
Venue
Cell Death & Differentiation
Publisher
Springer Science and Business Media LLC
Published
2016-10-14
Volume
23
Issue
12
Pages
1961-1972
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
DOI
10.1038/cdd.2016.73
PMC
PMC5136485
OpenAlex
W2531781148
Cited by
24
References
1
Citations by year
2026: 3 · 2024: 6 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 2
FWCI
2.04
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Cell Death and Differentiation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
Funders
  • National Science Foundation
  • Deutsche Forschungsgemeinschaft
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (166473, 146181, 310030)
Topics
  • Health Sciences › Medicine › Rheumatology › Eosinophilic Disorders and Syndromes
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords
RhoH, eosinophilopoiesis, eosinophil differentiation, GATA2, Rho kinase, hypereosinophilic syndrome, bone marrow progenitor cells, eosinophilic leukemia, transcriptional regulation, Rho GTPases
MeSH terms
Animals, Bone Marrow, Cell Count, Cell Cycle, Cell Differentiation, Cell Movement, Cell Survival, Cells, Cultured, Chimera, Eosinophils, Humans, Longevity, Mice, Inbred C57BL, Phenotype, Transcription Factors, Interleukin-5, Up-Regulation, Immunophenotyping, Mice, Knockout, rho GTP-Binding Proteins, GATA2 Transcription Factor, Receptors, Interleukin-5

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