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Blood and airway eosinophilia represent markers for the endotype-driven treatment of allergic asthma. Little is known on mechanisms that link eosinophils and airway epithelial cells before and after these cells are infiltrated by eosinophils during allergic response. Given that innate immune mechanisms, mainly mediated by epithelial-derived cytokines (IL-33, IL-25, TSLP), induce eosinophil-maturing/attractive substances, we thought to evaluate the crosstalk between eosinophils and airway epithelial cells in the context of IL-33-mediated allergic inflammation. DUOX1 was previously described in clinically relevant aspects of allergic inflammation in a HDM -induced allergic asthma mice model, and in patients with chronic sinusitis or allergic asthma. Thus, we evaluated the involvement of HDM and eosinophils in the regulation of DUOX1 in airway epithelial cells. To recapitulate the lung environment present at the allergen challenge time in acute asthma, we set up an in vitro model based on murine bone marrow-derived eosinophils differentiated with IL-5 and then activated with IL-33 (EOs33) and TC1 or C57 airway epithelial cells. We found that treatment of epithelial cells with HDM induced an eosinophil-attractive environment and increased DUOX1 expression. Importantly, we found that the co-culture of airway epithelial cells with EOs33 or with conditioned medium from EOs33 enhanced the expression of DUOX1, which was further increased by combined stimulation (HDM plus EOs33). Our results suggest that lung recruited EOs once activated by IL-33 could be involved in a crosstalk loop with airway epithelial cells by DUOX1-mediated IL-33 secretion., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Immune cell-derived extracellular vesicles (EV) affect tumor progression and hold promise for therapeutic applications. Eosinophils are major effectors in Th2-related pathologies recently implied in cancer. Here, we evaluated the anti-tumor activities of eosinophil-derived EV following activation with the alarmin IL-33. We demonstrate that IL-33-activated mouse and human eosinophils produce higher quantities of EV with respect to eosinophils stimulated with IL-5. Following incorporation of EV from IL-33-activated eosinophils (Eo33-EV), but not EV from IL-5-treated eosinophils (Eo5-EV), mouse and human tumor cells increased the expression of cyclin-dependent kinase inhibitor (CDKI)-related genes resulting in cell cycle arrest in G0/G1, reduced proliferation and inhibited tumor spheroid formation. Moreover, tumor cells incorporating Eo33-EV acquired an epithelial-like phenotype characterized by E-Cadherin up-regulation, N-Cadherin downregulation, reduced cell elongation and migratory extent in vitro, and impaired capacity to metastasize to lungs when injected in syngeneic mice. RNA sequencing revealed distinct mRNA signatures in Eo33-EV and Eo5-EV with increased presence of tumor suppressor genes and enrichment in pathways related to epithelial phenotypes and negative regulation of cellular processes in Eo33-EV compared to Eo5-EV. Our studies underscore novel IL-33-stimulated anticancer activities of eosinophils through EV-mediated reprogramming of tumor cells opening perspectives on the use of eosinophil-derived EV in cancer therapy., (© 2024. The Author(s).)

Trogocytosis is a cellular process whereby a cell acquires a membrane fragment from a donor cell in a contact-dependent manner allowing for the transfer of surface proteins with functional integrity. It is involved in various biological processes, including cell-cell communication, immune regulation, and response to pathogens and cancer cells, with poorly defined molecular mechanisms. With the exception of eosinophils, trogocytosis has been reported in most immune cells and plays diverse roles in the modulation of anti-tumor immune responses. Here, we report that eosinophils acquire membrane fragments from tumor cells early after contact through the CD11b/CD18 integrin complex. We discuss the impact of trogocytosis in innate immune cells on cancer progression in the context of the evidence that eosinophils can engage in trogocytosis with tumor cells. We also discuss shared and cell-specific mechanisms underlying this process based on in silico modeling and provide a hypothetical molecular model for the stabilization of the immunological synapse operating in granulocytes and possibly other innate immune cells that enables trogocytosis., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)