Alison May, PhD

The respiratory submucosal glands (SMGs) are responsible for protecting our lungs by producing airway mucus, which traps inhaled harmful organisms from our surrounding environment. Significant changes in SMGs occur in patients with diseases such as cystic fibrosis, asthma and COPD. Abnormally functioning SMGs secrete thickened mucus that cannot be cleared. This results in airway blockage, infection and inflammation. Recent evidence indicates that macrophages, a cell type of the immune system, are critical in repairing and regenerating airway tissue after injury. But we don’t know if, and how, these cells interact and signal to SMGs. To understand immune-gland interactions in the airway, we aim to define how macrophages promote the development and formation of SMGs, and how they regulate mechanisms needed to establish different SMG cell types. Understanding this relationship will give substantial insight into gland development, with the aim of identifying new treatments for glandular repair in airway disease.

Update: Our research has revealed new roles for tissue-resident macrophages—cells that are essential for repair and regeneration of the lung and airway—in submucosal gland development in the airway. Using advanced imaging and genetic tools, we identified a specialized population of macrophages within developing airway glands and observed that these cells closely interact with all major glandular cell types. We found that loss of the immune signaling molecule TNF disrupts normal gland formation, highlighting a previously unrecognized developmental role for this traditionally pro-inflammatory pathway. This work will establish a critical framework for our future investigations into the cellular and molecular mechanisms governing SMG development and its disruption in disease.