Top-level science through the eyes of an expert.

The fifth webinar in the Naked Immunology series is now scheduled on June 30, 2023 at 8 a.m. (PST), 11 a.m. (EST), 5 p.m. (CET). The webinar is open to English-speaking participants with a solid scientific background. Featured speaker is Dr. Cezmi Akdis, the director of the Swiss Institute of Allergy and Asthma Research (SIAF) in Davos and Professor in Zurich University Medical Faculty.

Humans and many domestic and wild animals are exposed to a variety of toxins and chemicals every day. It is estimated that more than 350,000 new chemicals have been introduced to our lives, mostly without any reasonable control of their toxicity during the last 60 years. There is a plethora of studies pointing to the rapid rise of disease prevalences linked to the exposure to many of these harmful substances during this period with their implications on disturbed skin and mucosal epithelial barrier functions. According to the epithelial barrier theory, exposure to many of these substances damages the epithelium on skin, lung and intestine and together with the involvement of microbiome and immune system a chronic inflammation develops in the affected organs and even in distant organs. Extensive evidence is being developed in our lab by screening more than 100 epithelial barrier disruptor molecules.

Recently developed methods representing as close as possible to human tissues, such as human native skins, lung, gut and skin organoids, organs-on-a-chip, induced pluripotent stem cells, targeted and non-targeted proteomics, spatial and single cell transcriptomics, and electric impedance spectroscopy are being used. Mouse models have been performed to support the in vivo relevance of these human 3D tissue-based assays. Many ingredients of laundry and dishwasher detergents, rinse aids, toothpastes, shampoos, house-hold cleaners, particulate matter, processed food additives and emulsifiers have been studied. Their epithelial barrier damaging, and pro-inflammatory mechanisms have been identified as oxidative stress, inflammasome activation, apoptosis induction and direct interference and damage to epithelial barrier forming molecules.

To heal, slow down or mitigate their barrier disrupting effects, more than 20 candidate rescue molecules have been identified and used in experiments with pre-exposure and during exposure to disruptors. Decreased release of epithelial alarmins and a wide range of other proinflammatory cytokines and chemokines, protection of the epithelial barrier integrity, and decreased oxidative stress have been achieved by selected classes of rescue molecules. These data demonstrate the effect of direct epithelial barrier disruptor molecules and their mechanisms of action analyzed in human and mouse models. In addition, it opens a possibility to heal damaged epithelial barriers by pathway-specific compounds.