Cardiopulmonary and Immune Alterations in the Ts65Dn Mouse Model of Down Syndrome and Modulation by Epigallocatechin-3-Gallate-Enriched Green Tea Extract

<b>Background/Objectives</b>: Cardiovascular and pulmonary diseases are leading comorbidities n individuals with Down syndrome (DS). Although clinically well described, preclinical models fully characterizing these cardiopulmonary alterations are lacking. Our objective is to characterize the cardiopulmonary and immunological phenotype in a commonly used DS mouse model, the Ts65Dn mice, and investigate the modulatory effects of green tea extract enriched in epigallocatechin-3-gallate (GTE-EGCG); <b>Methods</b>: Treatment started at embryonic day 9 and continued until postnatal day (PD) 180. Mice were longitudinally monitored using micro-computed tomography, and structural, functional, and immunological alterations were evaluated at PD210 to determine the persistent effects of GTE-EGCG administration; <b>Results</b>: Ts65Dn mice displayed normal structural lung development and presented with right ventricular hypertrophy and reduced B-cell lymphocytes, indicating that this model may find applications in immunological respiratory research specific to the context of DS. GTE-EGCG administration induced transient lung immaturity, persistent decreases in lung function, and airway hyperreactivity, while normalizing arterial and right ventricular morphology and partially restoring B-cell lymphocyte numbers; <b>Conclusions</b>: These findings underscore the dual nature of EGCG modulation, both beneficial and adverse, and highlight the importance of a multiorgan, holistic approach when evaluating therapeutic interventions in DS models.