Dr. Jay Kolls
Professor of Medicine and Pediatrics, John W Deming Endowed Chair in Internal Medicine
Areas of Expertise
Biography
Dr. Jay K. Kolls is Professor of Medicine and Pediatrics, the John W Deming Endowed Chair in Internal Medicine and Director, Center for Translational Research in Infection and Inflammation Tulane School of Medicine. Prior to his recruitment to Tulane he was Professor of Pediatrics and Director of the Richard King Mellon Foundation Institute for Pediatric Research at the Children Hospital of Pittsburgh/UPMC. He earned his medical degree at the University of Maryland and completed his residency training in Internal Medicine/Pediatrics at Charity Hospital in New Orleans, LA. After that he completed Fellowships in Adult and Pediatric Pulmonology at LSU and Tulane Health Sciences Center respectively. He performed his research fellowship in the laboratory of Dr. Bruce Beutler at Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX. Dr Kolls was recruited in July 2003 to the Children’s Hospital of Pittsburgh at the University of Pittsburgh in Pittsburgh, Pennsylvania where he was Division Chief of Pediatric Pulmonary Medicine and named the inaugural Niels K Jerne Professor Pediatrics and Immunology in 2007. Dr. Kolls has been member of the American Thoracic Society since 1989. He is also a member of the American Association of Immunology, American Society of Microbiology, American Society of Clinical Investigation, and the Association of American Physicians. Dr. Kolls has authored or co-authored more than 250 peer-reviewed articles. The major goal of Dr. Kolls’ research is to investigate mechanisms of mucosal host defenses in the lung in normal and immunocompromised hosts using genetic models. Presently, his lab is investigating how IL-23 and IL-17 and IL-22 regulate host defense against extracellular pathogens and epigenetic regulation of macrophage function. Additionally, he researches host susceptibility to opportunistic infection such as Pneumocystis and is developing novel therapies against this pathogen. Dr. Kolls has been co-Chair and Chair of the Gordon Conference on the biology of Acute Respiratory Infection and has co-organized a Keystone symposia on Th17 cells and Asthma and COPD.
Education
University of Maryland
Articles
Targeting the IL-22/IL-22BP axis enhances tight junctions and reduces inflammation during influenza infection
2019
The seasonal burden of influenza coupled with the pandemic outbreaks of more pathogenic strains underscore a critical need to understand the pathophysiology of influenza injury in the lung. Interleukin-22 (IL-22) is a promising cytokine that is critical in protecting the lung during infection. This cytokine is strongly regulated by the soluble receptor IL-22-binding protein (IL-22BP), which is constitutively expressed in the lungs where it inhibits IL-22 activity. The IL-22/IL-22BP axis is thought to prevent chronic exposure of epithelial cells to IL-22. However, the importance of this axis is not understood during an infection such as influenza. Here we demonstrate through the use of IL-22BP-knockout mice (il-22ra2−/−) that a pro-IL-22 environment reduces pulmonary inflammation during H1N1 (PR8/34 H1N1) infection and protects the lung by promoting tight junction formation. We confirmed these results in normal human bronchial epithelial cells in vitro demonstrating improved membrane resistance and induction of the tight junction proteins Cldn4, Tjp1, and Tjp2. Importantly, we show that administering recombinant IL-22 in vivo reduces inflammation and fluid leak into the lung. Taken together, our results demonstrate the IL-22/IL-22BP axis is a potential targetable pathway for reducing influenza-induced pneumonia.
Follistatin-like 1 Attenuation Causes Spontaneous Smoke-Resistant Pulmonary Emphysema
2019
The role of follistatin-like 1 (FSTL-1) in lung homeostasis is unknown. Objectives: We aimed to define the impact of FSTL-1 attenuation on lung structure and function and identify FSTL-1-regulated transcriptional pathways in the lung. Further, we aimed to analyze the association of FSTL1 SNPs with lung disease. Methods: FSTL-1 hypomorphic mice (FSTL-1 Hypo) underwent lung morphometry, pulmonary function testing and micro-CT. Fstl1 expression was determined in wild-type lung cell populations from three independent research groups. RNA sequencing of wild-type and FSTL-1 Hypo mice identified FSTL-1-regulated gene expression, followed by validation and mechanistic in vitro examination. FSTL1 SNP analysis was performed in the COPDGene cohort. Measurements and Main Results: FSTL-1 hypomorphic mice developed spontaneous emphysema, independent of smoke exposure. Fstl1 is highly expressed in the lung by mesenchymal and endothelial cells, but not immune cells. RNA sequencing of whole lung identified 33 FSTL-1-regulated genes, including Nr4a1, an orphan nuclear hormone receptor that negatively regulates NF-κB signaling. In vitro, recombinant FSTL-1 treatment of macrophages attenuated NF-κB p65 phosphorylation in an Nr4a1-dependent manner. Within the COPDGene cohort, several SNPs in the FSTL1 region corresponded to COPD and lung function. Conclusions: This work identifies a novel role for FSTL-1 protecting against emphysema development independent of smoke exposure. This FSTL-1-deficient emphysema implicates regulation of immune tolerance in lung macrophages through Nr4a1. Further study of the mechanisms involving FSTL-1 in lung homeostasis, immune regulation and NF-κB signaling may provide additional insight into the pathophysiology of emphysema and inflammatory lung diseases.
Biomarkers that differentiate false positive urinalyses from true urinary tract infection
2019
The specificity of the leukocyte esterase test (87%) is suboptimal. The objective of this study was to identify more specific screening tests that could reduce the number of children who unnecessarily receive antimicrobials to treat a presumed urinary tract infection (UTI).
Intestinal IL-17R Signaling Constrains IL-18-Driven Liver Inflammation by the Regulation of Microbiome-Derived Products
2019
Interleukin (IL)-17 signaling to the intestinal epithelium regulates the intestinal microbiome. Given the reported links between intestinal dysbiosis, bacterial translocation, and liver disease, we hypothesize that intestinal IL-17R signaling plays a critical role in mitigating hepatic inflammation. To test this, we study intestinal epithelium-specific IL-17RA-deficient mice in an immune-driven hepatitis model. At the naive state, these mice exhibit microbiome dysbiosis and increased translocation of bacterial products (CpG DNA), which drives liver IL-18 production. Upon disease induction, absence of enteric IL-17RA signaling exacerbates hepatitis and hepatocyte cell death. IL-18 is necessary for disease exacerbation and is associated with increased activated hepatic lymphocytes based on Ifng and Fasl expression. Thus, intestinal IL-17R regulates translocation of TLR9 ligands and constrains susceptibility to hepatitis. These data connect enteric Th17 signaling and the microbiome in hepatitis, with broader implications on the effects of impaired intestinal immunity and subsequent release of microbial products observed in other extra-intestinal pathologies.
Interleukin-22 (IL-22) Binding Protein Constrains IL-22 Activity, Host Defense, and Oxidative Phosphorylation Genes during Pneumococcal Pneumonia
2019
Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide, and interleukin-22 (IL-22) helps contain pneumococcal burden in lungs and extrapulmonary tissues. Administration of IL-22 increases hepatic complement 3 and complement deposition on bacteria and improves phagocytosis by neutrophils. The effects of IL-22 can be tempered by a secreted natural antagonist, known as IL-22 binding protein (IL-22BP), encoded by Il22ra2. To date, the degree to which IL-22BP controls IL-22 in pulmonary infection is not well defined. Here, we show that Il22ra2 inhibits IL-22 during S. pneumoniae lung infection and that Il22ra2 deficiency favors downregulation of oxidative phosphorylation (OXPHOS) genes in an IL-22-dependent manner. Il22ra2−/− mice are more resistant to S. pneumoniae infection, have increased IL-22 in lung tissues, and sustain longer survival upon infection than control mice. Transcriptome sequencing (RNA-seq) analysis of infected Il22ra2−/− mouse lungs revealed downregulation of genes involved in OXPHOS. Downregulation of this metabolic process is necessary for increased glycolysis, a crucial step for transitioning to a proinflammatory phenotype, in particular macrophages and dendritic cells (DCs). Accordingly, we saw that macrophages from Il22ra2−/− mice displayed reduced OXPHOS gene expression upon infection with S. pneumoniae, changes that were IL-22 dependent. Furthermore, we showed that macrophages express IL-22 receptor subunit alpha-1 (IL-22Ra1) during pneumococcal infection and that Il22ra2−/− macrophages rely more on the glycolytic pathway than wild-type (WT) controls. Together, these data indicate that IL-22BP deficiency enhances IL-22 signaling in the lung, thus contributing to resistance to pneumococcal pneumonia by downregulating OXPHOS genes and increasing glycolysis in macrophages.
Media Appearances
Can too much salt lead to bad skin?
“Th17 cells are critical for fighting extracellular pathogens — yeast and certain bacterial infections — that largely live outside our cells, particularly on mucosal surfaces like in the mouth or GI tract,” said Dr. Jay Kolls, a professor of medicine and pediatrics at Tulane University, who wasn’t involved in the study.
