Carolina Ballester Lopez, PhD student in Ali Önder Yildirim's Lab ”Immunopathology of COPD” at the ILBD/CPC received an International Trainee Scholarship Award for 2018 from the American Thoracic Society (ATS). This award provides support to attend the ATS International Conference in San Diego, CA, and includes a one year In-Training Membership. Carolina Ballester Lopez's abstract with the title “The Novel Notch Ligand DNER Modulates IFNγ Levels in Recruited Macrophages by Enhancing Non-Canonical Notch During COPD Progression” was chosen as an oral presentation in the Mini Symposium session “Asthma and COPD – the best of respiratory structure and function”, which will take place on May 23, 2018.
Abstract - In the last decades it has become more evident that chronic inflammation plays a pivotal role in the progression of chronic obstructive pulmonary disease (COPD). Nevertheless, the underlying pathways that drive and exacerbate the disease remain unclear. A novel non-canonical Notch ligand, DNER (Delta/Notch-like Epidermal Growth Factor (EGF)-related Receptor), has been shown in a genome-wide association study (GWAS) to correlate with GOLD stages (Hancock et al. PLoS Genet 2012). We identified that DNER expression is increased in COPD patients compared to healthy lungs and mainly localized to macrophages. In in vivo studies, immunofluorescence revealed lower nuclear translocation of NICD1 in cigarette smoke-exposed Dner-/- vs WT mice alveolar macrophages that reduces a significantly lower F4/80+ SiglecF- IFNγ+ macrophage population in cigarette smoke exposed Dner-/- mice compared to WT. Together, DNER is a novel protein induced in COPD patients and chronic CS-exposed mice that regulates IFNγ secretion via non-canonical Notch signaling in pro-inflammatory recruited macrophages. These results provide a new pathway involved in COPD immunity that could contribute to the discovery of innovative therapeutic targets.