Jahrestagung der Gesellschaft fur Padiatrische Nephrologie.

The proceedings contain 92 papers. The topics discussed include: cellular and humoral immune responses after SARS-CoV-2 vaccination in pediatric kidney recipients;adult outcomes of childhood-onset idiopathic nephrotic syndrome: findings from a health insurance database;the genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies;translational profiling of developing podocytes during glomerulogenesis;MAGED2 is required under hypoxia for cAMP signaling by inhibiting MDM2-dependent endocytosis of G-Alpha-S;high throughput investigation of the metabolic flux of intact cortical kidney tubules;peritoneal membrane junction and solute transporter expression and function in health, CKD and PD;and Function and interaction of coronavirus ion channel proteins.

Microbial Dysbiosis and Epithelial Dysfunction in Vitamin A-Deficient Lungs

Once believed to be sterile, recent studies now show microbes inhabiting healthy lungs that are dysregulated in patients with chronic obstructive pulmonary disease (COPD), asthma, tuberculosis (TB), and SARS-CoV-2 infection. Other studies have shown an increase in pulmonary disease and recurrent respiratory infections in malnourished patients. According to the World Health Organization, vitamin A deficiency (VAD) is now a major public health issue in low-income communities and many developing countries. While VAD has been shown to alter gene expression and tissue morphology in humans and mice, research suggests the lung microbiome plays an intimate role in the metabolic regulation, pathogen inhibition, and inflammatory responses in the lung. Whether dysbiosis is a cause or consequence of chronic respiratory conditions, or whether retinoic acid (RA) - the bioactive metabolite of Vitamin A - is essential for lung microbiome homeostasis, remains unknown. Therefore, we hypothesize that dietary VAD leads to epithelial remodeling which promotes microbial dysbiosis;the dysbiosis then perpetuates epithelial remodeling via host-microbe interactions. Our preliminary results show anatomical/pathological changes to the epithelium in VAD adult mouse lungs compared to controls (VAS). Using our Nkx2- 1creERT2/dnRAR Rosa26 tdTomato transgenic mouse model that selectively induces VAD in the adult lung epithelium following tamoxifen injections, our data supports the hypothesis that host epithelial aberration associated with dietary VAD is induced locally in the lung and not via distal or systemic mechanisms. Our data also indicates the onset of dysbiosis in adult mouse lungs as early as three weeks post-diet modulation as observed through changes in microbial composition in VAD mice compared to controls. Finally, our bulk RNAseq analysis of host and microbial gene signatures has uncovered mechanisms associated with microbial metabolic functions, ciliopathy, host cellular polarity, and immune response to infection, that are dysregulated in the absence of vitamin A. Further, we have also identified altered transcriptional activity of microbes that are traditionally symbiotic or pathobiotic under normal homeostasis. This work indicates the presence of specific host-microbe interactions that are essential for lung homeostasis and protection against lung infection and disease that are dysregulated or lost in the absence of dietary vitamin A.