Eosinophils restrain humoral alloimmunity after lung transplantation.

Autor:	Mei Z; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Khalil MA; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Guo Y; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Li D; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Banerjee A; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Terada Y; Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, USA., Yokoyama Y; Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, USA., Kratzmeier C; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Chen K; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Li L; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Lau CL; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA., Courneya JP; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA., Luzina IG; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA., Atamas SP; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA., Gelman AE; Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, USA.; Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, Missouri, USA., Kreisel D; Department of Surgery, Washington University in St. Louis, St. Louis, Missouri, USA.; Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, Missouri, USA., Jacobsen EA; Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic, Scottsdale, Arizona, USA., Krupnick AS; Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2024 Feb 08; Vol. 9 (3). Date of Electronic Publication: 2024 Feb 08.
DOI:	10.1172/jci.insight.168911
Abstrakt:	While the function of many leukocytes in transplant biology has been well defined, the role of eosinophils is controversial and remains poorly explored. Conflicting data exist regarding eosinophils' role in alloimmunity. Due to their prevalence in the lung, and their defined role in other pulmonary pathologies such as asthma, we set out to explore the role of eosinophils in the long-term maintenance of the lung allograft. We noted that depletion of eosinophils results in the generation of donor-specific antibodies. Eosinophil depletion increased memory B cell, plasma cell, and antibody-secreting cell differentiation and resulted in de novo generation of follicular germinal centers. Germinal center formation depended on the expansion of CD4+Foxp3-Bcl6+CXCR5+PD-1+ T follicular helper (Tfh) cells, which increase in number after eosinophil depletion. Mechanistically, we demonstrate that eosinophils prevent Tfh cell generation by acting as the dominant source of IFN-γ in an established lung allograft, thus facilitating Th1 rather than Tfh polarization of naive CD4+ T cells. Our data thus describe what we believe is a unique and previously unknown role for eosinophils in maintaining allograft tolerance and suggest that indiscriminate administration of eosinophil-lytic corticosteroids for treatment of acute cellular rejection may inadvertently promote humoral alloimmunity.
Databáze:	MEDLINE
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