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Title : Allergen-Stimulated Release of Genomic DNA Fragments Function as Alarmins which Augment Type 2 Immunity in Airways
Name : Scott M O'Grady
University : University of Minnesota
Country : USA
Download AbstractAbstract:
Airway exposure to environmental allergens activates cellular stress pathways resulting in the release of danger signals known as alarmins. Allergens associated with the saprophytic fungus, Alternaria alternata exacerbate airway inflammation in sensitized asthma patients. Exposure of the airway epithelium to Alternaria induces oxidative stress, leading to the secretion of ATP, a primary alarmin that stimulates Ca2+ uptake, producing sustained increases in intracellular [Ca2+]. In the present study, we examined the mechanisms responsible for allergen-evoked DNA fragmentation and release from human airway epithelial cells and determined the role of extracellular DNA (eDNA) in type 2 immunity. Human bronchial epithelial (hBE) cells were used to investigate allergen-evoked DNA mobilization and release using comet assays to measure DNA fragmentation, double-stranded DNA assays to measure the kinetics of eDNA release, and DNA sequencing to determine eDNA composition. The role of eDNA in type 2 immunity was investigated in mice following intranasal exposure to Alternaria.
Alternaria extract rapidly stimulated mitochondrial and nuclear DNA release from hBE cells, whereas mitochondrial DNA, but not nuclear DNA release, was induced by house dust mite extract. Alternaria-induced increases in intracellular [Ca2+] activated the pro-protein convertase enzyme furin, which in turn produced non-canonical activation of caspase-3, ultimately leading to nuclear DNA fragmentation as shown in comet assays. eDNA displayed disproportionally higher amounts of promotor and exon sequences and lower intron and intergenic regions compared to predictions of random DNA fragmentation, indicating that the eDNA release was not a consequence of epithelial cell ETosis. In mice, pretreatment with polyamidoamine dendrimers, which function as DNA scavengers, blocked Alternaria-evoked type 2 immune responses. Furthermore, in caspase-3-deficient mice, Alternaria-stimulated eDNA release was inhibited. Lastly, co-administration of mouse genomic DNA along with Alternaria extract amplified IL-5 and IL-13 secretion into bronchoalveolar lavage fluid, whereas DNA alone produced no response. In conclusion, these results describe a previously unknown, allergen-stimulated mechanism of rapid genomic DNA release that augments type 2 immunity in airways.
Keywords: Alternaria; house dust mite; alarmins; extracellular DNA; Asthma; allergic inflammation.
Biography:
Scott M. O’Grady, currently affiliated with the University of Minnesota, Minneapolis/St. Paul, MN, is a distinguished researcher in the fields of Cell Physiology & Biophysics. Dr. O’Grady’s educational journey includes a Ph.D. in Physiology from the Department of Physiology and Biophysics at the University of Illinois, Urbana-Champaign. He received further training in epithelial ion transport during his Postdoctoral Fellowship at the University of Chicago, and as a Research Associate in the Department of Medicine at Columbia University, New York, NY. Dr. O’Grady’s research interests primarily revolve around understanding the intricate mechanisms and regulation of electrolyte transport across epithelial tissues, focusing primarily on airways. His laboratory also investigates innate immune function of the airway epithelium in relation to cystic fibrosis, asthma, and allergic airway disease. Collaborating with Dr. Hirohito Kita from the Mayo Clinic, they explore the role of the airway epithelium in allergic inflammation induced by environmental allergens and fungal lung infections. Dr. O’Grady’s dedication to advancing scientific knowledge is evident through his numerous honors and awards, including recognition in prestigious journals such as the Journal of Allergy and Clinical Immunology, Journal of Physiology and the American Journal of Physiology [Cell Physiology]. Additionally, he has contributed significantly to editorial service, serving on the editorial boards of the International Journal of Molecular Sciences, American Journal of Physiology [Cell Physiology], and International Archives of Clinical Pharmacology. His commitment to excellence extends beyond research, as evidenced by his teaching excellence award from the College of Veterinary Medicine at the University of Minnesota.
Title : Paraptosis and tumor immunity
Name : H Terry Wepsic
University : University of California Irvine
Country : USA
Download AbstractDr. Wepsic is a physician/pathologist with a specialty in cancer biology and tumor immunology. When a cancer researcher chooses proton therapy to treat his prostate cancer, it speaks volumes about the efficacy of this treatment option. He is a 61-year-old academic pathologist/hospital administrator with Long Beach VA Hospital and Associate Dean for Research at the University of California Irvine. His research specialty is tumor immunology and tumor biology. He had a rich and very interesting academic career and have published many manuscripts in cancer immunology.
Title : Cutaneous Findings in Inborn Errors of Immunity: An Immunologist's Perspective
Name : Deniz Cagdas
University : Hacettepe İhsan Doğramacı Children's Hospital
Country : Turkey
Download AbstractInstitutional Information:
Prof. Deniz is a Faculty of Medicine (Turkish) at Hacettepe İhsan Doğramacı Children’s Hospital.
Research Areas: Her research areas include Medicine, Medical Biology, Internal Medicine Sciences, Child Health and Diseases, Pediatric Cardiology, Pediatric Immunology and Allergy, Genetic Disorders, Health Sciences, and Fundamental Medical Sciences.
Prof. Deniz is a Faculty of Medicine (Turkish) at Hacettepe İhsan Doğramacı Children’s Hospital.
Research Areas: Her research areas include Medicine, Medical Biology, Internal Medicine Sciences, Child Health and Diseases, Pediatric Cardiology, Pediatric Immunology and Allergy, Genetic Disorders, Health Sciences, and Fundamental Medical Sciences.
Title : Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy
Name : Tatiani Uceli Maioli
University : Federal University of Minas Gerais
Country : Brazil
Download AbstractTatiani MAIOLI is a Assistant Professor at Federal University of Minas Gerais, Belo Horizonte in Brazil. Tatiani Uceli Maioli is an academic researcher. The author has contributed to research on topics: FGF21 and natural killer T cell. The author has an index of 1, and co-authored 1 publication receiving 271 citations.
Title : Podcasting in Clinical Allergy and Immunology: Our Experience and a Review of the Current Landscape
Name : Payel Gupta
University : LifeMD
Country : USA
Download AbstractHighlights
Triple Board Certified in Allergy & Immunology, Internal Medicine, and Pediatrics.
Clinical Instructor at Mount Sinai Medical Center, NY, and Assistant Clinical Professor at SUNY Downstate Medical Center, NY.
Medical Director for Allergy, Asthma, Immunology & ENT for LifeMD.com.
Experience and Education
Dr. Payel Gupta completed her undergraduate studies at the University of Michigan in Ann Arbor and majored in biopsychology and religion. She earned her medical degree from the College of Human Medicine at Michigan State University and then pursued a residency in both Internal Medicine and Pediatrics at the Rush University Medical Center in Chicago. She then moved to New York City and did a fellowship in allergy and immunology at the State University of New York, Downstate Medical Center.
She is practicing in New York City treating both adult and pediatric patients with asthma, environmental allergies, allergic skin conditions, immune disorders, and food allergies. She is the Medical Director of Allergy, Asthma, Immunology & ENT for LifeMD.com, owner of Ease Allergy (easeallergy.com), and co-founded getcleared.com.
She is a member of a number of professional organizations including the American Academy of Allergy, Asthma and Immunology and the American College of Allergy and Immunology (ACAAI), where she serves as the Chair of the Integrative Medicine Committee and is a member of the Telemedicine and Technology Taskforce. She is past-president of the New York Allergy and Asthma Society and a Volunteer National Spokesperson for the American Lung Association. She is also a Co-Host on The Itch Podcast (www.itchpodcast.com), a podcast dedicated to helping patients and providers understand allergic conditions.
DISCLOSURES: Dr. Gupta has received contracts and grants from the Asthma and Allergy Network, consulting fees from Johnson & Johnson, honoraria for lectures from the American College of Allergy, Asthma & Immunology and ALK, and support for attending meetings from the American College of Allergy, Asthma & Immunology. She has been on an Advisory Board for Blueprint Pharmaceuticals and Sanofi. And has stock options at LifeMD.