The pulmonary landscape of the lung presents a unique challenge as a toxicological target in that it is extremely diverse, being comprised of several (over 40!) cell types. While the most important function of the lung is its role in gas exchange, the lung is also charged with a vital role in immune defense, with epithelial cells and macrophages maintaining lung homeostasis.
The Symposium Session on “Immune-Epithelial Cell Crosstalk in Lung Toxicology and Disease” at the 2019 Annual Meeting and ToxExpo provided a comprehensive overview of how critical epithelial-immune crosstalk is in the regulation of pulmonary response to toxicants.
There are several challenges associated with investigating the crosstalk between cells after toxicant exposure, many of which are precluded by the lack of an appropriate model to study the disease. Dr. Alessandro Venosa highlighted the role of epithelial type II cell stress in the initiation and modulation of pulmonary inflammation through crosstalk with resident and peripheral inflammatory subsets (including macrophages) after chronic exposure, using a novel inducible transgenic mouse model. Dr. Yang Jin illuminated the audience on the emerging role that extracellular vesicles play in acute liver injury. Dr. Shaun McCullough further educated the audience on the impact of chromatin remodeling and the subsequent epigenetic environment on specific responses to air pollutants (particularly ozone), which are in turn associated with exacerbation of inflammatory conditions.
An important takeaway from the session, as highlighted by Dr. Kymberly Gowdy, was that several distinct macrophage populations have been identified in the lung (e.g., tissue-resident versus interstitial versus monocyte-derived alveolar macrophages), each with different ontogenies, functions, and differential responses to toxicants. Ozone, for example, was found to alter specifically tissue-resident alveolar macrophage morphology-induced cytokine expression. Additionally, lipid metabolism was also altered differentially in tissue-resident versus interstitial macrophages. There is clearly no “one-macrophage-fits-all” when it comes to the lung, and which cell subtype is involved in the mechanism of toxicant-specific injury is certainly something that must not be overlooked.
Finally, in a cautionary message by Dr. Laura Van Winkle, the audience was reminded of the enormous roles species, age, sex, history of prior exposure, cell-type/site-specific insults, and antioxidant status play in lung epithelial cell response to nanoparticles, ozone, naphthalene, and particulate matter. Each of these needs to be carefully considered when designing experiments to study immune-epithelial cell crosstalk in order to gain an accurate perspective and generate relevant data.
The session certainly resonated with me, as I am involved in investigating the role of immune cells in response to inhaled toxicants. More than that, however, the session gave the audience an appreciation for and a better understanding of the different cellular systems that exist within the lung and how signaling between these systems is critical in determining the consequences of toxicant exposure.
This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.