Eosinophils ameliorate chronic lung allograft dysfunction through alteration of the cytokine microenvironment of the allograft 3628

Abstract Description The main barrier to long-term survival of the lung allograft is the development of a fibrotic form of chronic rejection, known as chronic lung allograft dysfunction (CLAD). Human observational studies have identified high numbers of eosinophils in chronically rejected lungs. This association has led to the presumption that eosinophils may contribute to CLAD. To study this, we transplanted B10 minor antigen mismatched lungs into B6 recipients or mice rendered deficient in eosinophils though the deletion of GATA1. Unexpectedly, we noted that markers of CLAD; airway obliteration (17.3±2.3), peri-airway fibrosis (1.8±0.7), and lung parenchymal fibrosis (9.8±4), were substantially lower in the presence of eosinophils. Such data suggested that eosinophils ameliorate, rather than potentiate CLAD. Gene expression analysis revealed upregulation of pathways associated with Th17 polarization (IL-17a, IL-17Rα, ROR-gt, IL-6) in the absence of eosinophils. Further cytokine analysis demonstrated that eosinophils are the dominant source of IFNg in the chronically rejected lung allograft. Th17 has previously been linked to chronic rejection in multiple transplant models. Due to the antagonistic nature of Th1 and Th17, along with our current data, eosinophil-production of IFNg- may mediate Th1 rather than Th17 polarization to ameliorate CLAD. Our murine data suggests that augmenting or targeting eosinophils may be one method for improving clinical outcomes of chronic lung rejection. Funding Sources P01AI116501 NIH/NIAAD R01AI145108 NIH/NIAAD I01BX002299 VA/Merit R01HL166402 NIH/NHLBI Topic Categories Transplantation Immunology (TRAN)