Differential regulation of Type 1 and Type 2 mouse eosinophil activation by apoptotic cells

Avishay Dolitzky, Inbal Hazut, Shmulik Avlas, Sharon Grisaru-Tal, Michal Itan, Ilan Zaffran, Francesca Levi-Schaffer, Motti Gerlic, Ariel Munitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis, host defense and cancer. Although eosinophils have been studied mostly in the context of Type 2 inflammatory responses, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ. Notably, both Type 1- and Type 2 inflammatory environments are characterized by tissue damage and cell death. Collectively, this raises the possibility that eosinophils can interact with apoptotic cells, which can alter eosinophil activation in the inflammatory milieu. Herein, we demonstrate that eosinophils can bind and engulf apoptotic cells. We further show that exposure of eosinophils to apoptotic cells induces marked transcriptional changes in eosinophils, which polarize eosinophils towards an anti-inflammatory phenotype that is associated with wound healing and cell migration. Using an unbiased RNA sequencing approach, we demonstrate that apoptotic cells suppress the inflammatory responses of eosinophils that were activated with IFN-γ + E. coli (e.g., Type 1 eosinophils) and augment IL-4-induced eosinophil activation (e.g., Type 2 eosinophils). These data contribute to the growing understanding regarding the heterogeneity of eosinophil activation patterns and highlight apoptotic cells as potential regulators of eosinophil polarization.

Original languageEnglish
Article number1041660
JournalFrontiers in Immunology
Volume13
DOIs
StatePublished - 31 Oct 2022

Funding

FundersFunder number
Azrieli Foundation Canada-Israel2015045
Cancer Biology Research Center
Dotan Hemato Oncology fund
Richard Eimert Research Fund on Solid Tumors
US-Israel bi-national science foundation2015163
Israel Cancer Research Fund
United States - Israel Binational Science Foundation
Israel Cancer Association
Israel Science Foundation886/15, 542/20
Tel Aviv University
Azrieli Foundation

    Keywords

    • IFN-gamma
    • IL-4
    • allergy
    • apoptotic cells
    • eosinophils
    • inflammation

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