ATG5 promotes eosinopoiesis, but inhibits eosinophil effector functions.

Germic, Nina; Hosseini, Aref; Stojkov, Darko; Oberson, Kevin; Claus, Meike; Benarafa, Charaf; Calzavarini, Sara; Angelillo-Scherrer, Anne; Arnold, Isabelle C; Müller, Anne; Riether, Carsten; Yousefi, Shida; Simon, Hans-Uwe (2021). ATG5 promotes eosinopoiesis, but inhibits eosinophil effector functions. (In Press). Blood American Society of Hematology 10.1182/blood.2020010208

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Eosinophils are white blood cells contributing to the regulation of immunity and they are involved in the pathogenesis of numerous inflammatory diseases. In contrast to other cells of the immune system, no information is available about the role of autophagy in eosinophil differentiation and functions. In order to study the autophagic pathway in eosinophils, we generated conditional knockout mice in which Atg5 is deleted within the eosinophil lineage only (designated Atg5eoΔ mice). Eosinophilia was provoked by crossbreeding Atg5eoΔ mice with Il5 (IL-5) overexpressing transgenic mice (designated Atg5eoΔIl5tg mice). Deletion of Atg5 in eosinophils resulted in a dramatic reduction in the number of mature eosinophils in blood and in an increase of immature eosinophils in the bone marrow. Atg5-knockout eosinophil precursors exhibited reduced proliferation under both in vitro and in vivo conditions, but no increased cell death. Moreover, reduced differentiation of eosinophils in the absence of Atg5 was also seen in mouse and human models of chronic eosinophilic leukemia. Atg5-knockout blood eosinophils demonstrated augmented levels of degranulation and bacterial killing in vitro. Moreover, in an experimental in vivo model, we observed that Atg5eoΔ mice achieve better clearance of the local and systemic bacterial infection with Citrobacter (C.) rodentium. Evidence for increased degranulation of ATG5low-expressing human eosinophils was also obtained in both tissues and blood. Taken together, mouse and human eosinophil hematopoiesis and effector functions are regulated by ATG5 which controls the amplitude of overall antibacterial eosinophil immune responses.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Faculty Institutions > Teaching Staff, Faculty of Medicine
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Germic, Nina; Hosseini, Aref; Stojkov, Darko; Oberson, Kevin; Claus, Meike Janina; Benarafa, Charaf; Calzavarini, Sara; Angelillo, Anne; Riether, Carsten; Yousefi, Shida and Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
600 Technology > 630 Agriculture

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

25 Feb 2021 15:09

Last Modified:

25 Feb 2021 15:09

Publisher DOI:

10.1182/blood.2020010208

PubMed ID:

33598715

BORIS DOI:

10.48350/152682

URI:

https://boris.unibe.ch/id/eprint/152682

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