- Aanvrager: J.A.A. Schrumpf Ing
ERS congress Paris, 15-19 September, 2018 JA Schrumpf, Department of Pulmonology, Leiden, the Netherlands
A summary of a visit to the ERS congress Paris, 15-19 September, 2018
JA Schrumpf, Department of Pulmonology, Leiden, the Netherlands
The Lung Foundation, Netherlands (grant # 5.1.13.033)
The congress for me started on a sunny Saturday September 15 with the opening ceremony. Science finally begun the day after with a nice symposium about recent developments in the field of stem cells and organoids. Jeffrey Beekman nicely showed us how organoids are cultured and used to assess whether patients with cystic Fibrosis might benefit from certain targeted treatment. Furthermore in this session, there was a talk by Melanie Koningshof about Broncho spheres, which are 3D cultures of bronchial epithelial cells growing in a Matrigel. Presence of Wnt ligands are very important for initiation/formation of these organoids, whereas presence of retinoic acid might decrease organoid size (this was furthermore shown at a poster by John-Poul Ng-Blichfeldt.
The next session that was also quite interesting. It was an oral presentation session about airway epithelial differentiation and regeneration. Francois Carlier (from the group of Charles Pilette) gave a very interesting talk about the differences between air liquid interface cultures of the bronchial epithelium derived from healthy donors and donors with (severe COPD). A showed that the epithelial barrier function was decreased as well as luminal secretory IgA due to decreased expression of the polymeric Ig receptor that is responsible for transportation of both sIgA and sIgM. He also mentioned that in the COPD derived cultures, EMT markers were increased as well as the number of goblet cells. In the same session Martijn Nawijn showed results from single cell RNAseq were he compared bronchial biopsies/brushes derived from asthma patients to healthy controls. He showed in the epithelial cell cluster presence of two groups of basal cells: proliferating (KT13+) and non-proliferating, ciliated cells, secretory epithelial cells and Ionocytes (a novel cell type, recently reported in Nature). These Ionocytes are FoxI1 positive, ckit high and express CFTR and other ion channels indicating a function in ion transport. In asthma compared to healthy controls, the number of proliferating KT13+ cells was increased and there was a loss of mature ciliated cells. Martijn furthermore mentioned a platform called “Human Lung Cell Atlas” that aims to identify all cell types present in the lung.
The next very interesting session was about a very hot topic at this moment: “mitochondrial dysfunction as a driver of lung disease”. Silke Meiners was the first to kick off this meeting with a general introduction about mitochondria where she explained that mitochondrial that has many functions. The highlighted the role of mitochondria in innate immunity. Infection, disease, environmental exposures and aging can cause mitochondrial dysfunction, which damages the mitochondria. Mitochondrial damage can lead to mitochondrial death, thereby releasing of mitochondrial DAMPS. These DAMPs trigger pattern recognition receptors, thereby initiating innate immune response such as neutrophil chemotaxis, secretion of IL-1? and type I interferons. She also explained that PINK1 plays a central role in mitophagy (the removal of damaged mitochondria). Whereas PINK1 levels were decreased in IPF, the opposite was true for COPD. In the same session, Anna Mora nicely showed that ER stress causes a decrease in PINK1 through the presence of an AFT3 (that is increased upon ER stress) binding side on the promotor of PINK1. She also showed that AFT3 KO mice were protected against development of Fibrosis. PINK1 deficiency increases the release of mitochondrial DNA thereby increasing expression of the fibrotic cytokine TGF-?1 via activation of TLR9. This summarizes my personal highlight of my fist day.
Next day morning there was a very interesting symposium about cross-talk and the lung microenvironment, where Philip Hansbro gave a wonderful overview about the microbiome and the gut-lung axis. Microbiome was a very hot topic at the ERS this year, the same afternoon the session: “Microbiomes in respiratory disease Role of local and systemic microbiomes and the potential for manipulation” was organized. Hans Bisgaard kicked off by showing finally some interesting data about vitamin D (that the main interest of my PhD thesis). He first showed that abundance of bacteria in the airways of 1 month old children was associated with a higher prevalence of asthma. He furthermore showed that maternal fish oil (that also contains vitamin D) and vitamin D supplementation during pregnancy affected the airway microbiome of the children. He finally showed an interesting concept of bacteriophages. These might be promising new/old-school tool in order to kill bacteria (especially those that are broad-spectrum antibiotic resistant). In the same session Chris Carlsten showed some new data about the effects of E-cigarettes that impairs clearance of bacteria and viruses in mouse models. This might be mediated by cinnaldehyde that inhibits function of immune cells.
A new day at the congress kicked off with a session about accelerated aging in lungs. The final presentation of this session was by Peter Barnes showing us new therapeutic options to treat COPD via target various pathway related to cellular senescence. Examples of these new drugs are: senotytics that induce apoptosis of senescent cells or for example metformin that might reduce mTOR-mediated inhibition of Sirtuin-1 and -6 via stimulation of AMPK. In the afternoon, I finally presented my poster entitled “TGF-?1 affects epithelial vitamin D metabolism and expression of host defence peptides”. We showed that TGF-?1 affects vitamin D metabolism via increasing expression of CYP24A1, that degrades vitamin D and we showed that TGF-?1 reduces expression of both vitamin D-dependent and constitutive expressed host defence peptides/proteins.
My final congress day ended with an excellent morning symposium about host defence peptides starting with Donald Davidson showing that RSV was killed by the host defence peptide LL-37 by binding the viral envelope. Furthermore Gimano Amangalim where he discussed the role of host defence proteins of COPD and cystic fibrosis. He showed that in both diseases the epithelial host defence is impaired through via e.g. impaired expression/activity of antimicrobial peptides and CFTR. I really enjoyed this congress and off course the city of Paris and hope to attend next year in Madrid.