More than a Shield: The Secret Functions of Epithelial Cells in Homeostasis and Infections

Dear Colleagues,

For a long time, epithelial cells have been thought of as a physical barrier that protects the internal milieu of the body from external threats. This simplified view casts epithelial cells merely as a passive brick in a defensive wall. However, a growing body of evidence is rapidly dismantling this view, revealing that these cells are far more than just inert shields; they are specialized sentinels and dynamic regulators in the complicated dialogues of health and disease. In homeostasis, epithelial cells are engaged in sophisticated networks with each other and with other non-epithelial neighbors. They actively participate in several physiological processes, including nutrient absorption in the gut and controlling the mucus composition in the airways. They communicate with the resident microbiota and even shape its composition in order to keep the tissue in harmony. In the face of infection, these same cells transform into a specialized line of active immune defense. This functional shift is not just accidental. It is based on the fact that these cells are equipped with recognition receptors, allowing them to rapidly detect pathogens during infection. Upon the detection of pathogens, they unleash different defensive mechanisms: producing bioactive molecules such as ATP and acetylcholine from epithelial tuft cells, releasing antimicrobial peptides in the gingiva, activating nearby nerve fibers which project from jugular-nodose ganglion, and even recruiting immune cells to the site of infection in the trachea. To accomplish these functions, epithelial cells employ various activating and/or signaling mechanisms, such as activating the Trpm5-signaling within tuft cells in response to Pseudomonas aeruginosa infection. Thus, understanding the molecular mechanisms controlling these diverse epithelium-mediated functions is crucial for the development of new strategies for enhancing the epithelial cell functions or restoring tissue homeostasis and fighting infections.

This Special Issue, "More than a Shield: The Secret Functions of Epithelial Cells in Homeostasis and Infections”, aims to uncover the multifaceted roles of epithelial cells, revealing their hidden, unrecognized roles in health and disease. This Special Issue highlights the cutting-edge discoveries on epithelial cells, from their role as localized sentinels to their impact on physiology and immunity. From the gut to the lungs, and the skin to the reproductive tract, these discoveries uncover the relationship between epithelial dysfunction and the emergence of clinically relevant pathologies such as pulmonary cystic fibrosis or inflammatory bowel disease, offering, at the same time, insights into potential therapeutic options. Additionally, these studies provide mechanistic views on the role of epithelial cells in host–pathogen interactions and the downstream activating effects on immune and nerve cells.     

In this Special Issue, original research articles and reviews, both comprehensive and mini-reviews, are welcome. Research areas may include (but are not limited to) the following: methodological advances for studying epithelial cell functions and/or interactions, epithelial chemosensation and signaling, epithelial metabolic signaling, epithelial–microbiota crosstalk, epithelial barrier maintenance, epithelial dysfunction in chronic diseases, epithelial–immune interactions, neuro-epithelial–immune axis, cell intrinsic immunity, role of epithelial cells as regulators of inflammation, bacterial infections of epithelial or mucosal tissues, epithelial cells as pathogen reservoirs, epithelium-associated inflammatory and metabolic diseases, and therapeutic targeting of epithelial cells.

I look forward to receiving your contributions.

Dr. Mohamed Ibrahem Elhawy
Dr. Na Zhao
Guest Editors

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• epithelial diversity
• signaling
• homeostasis
• immunity
• infection
• microbiome
• inflammation
• cytokines
• antimicrobial peptides