Emulating Immune Dysregulation by Trisomy 21 in a Multi-Organ-on-a-Chip System

Recurrent respiratory infections are particularly common in individuals with Down syndrome and are often life-threatening. Thus, it is important to understand the mechanisms by which the additional genetic material in Down syndrome impacts lung immune activity and response to respiratory pathogens; this would enable us develop/repurpose therapeutics that can protect people with Down syndrome against pulmonary infections. Here, we will apply organ-on-chip technology and develop a physiologically relevant murine and human stem cell-derived model of lung-bone marrow axis to delineate the impact of trisomy 21 on homeostatic physiology of lung, development of immune dysregulation, and presence (if any) and mechanisms of hyperreactivity to inhaled influenza virus infection.