Tissue-resident immune cells in asthma: drivers of inflammation, memory, and airway remodeling

The complex inflammatory condition associated with airflow obstruction and variable airway hyperresponsiveness (AHR) is a characteristics condition of asthma. Exposure of the lungs to different environmental triggers, such as allergens, pollen, and environmental toxicants, exaggerates the immune reaction, narrowing the airways and resulting in episodes of reversible bronchoconstriction. The interaction of resident immune cells, structural cells, and altered extracellular matrix proteins creates persistent inflammatory condition in lung, resulting in airways inflammation, hyperresponsiveness, and remodelling. The imbalance between pro-inflammatory and anti-inflammatory response from granulocytes, monocytes, and lymphocytes, along with an imbalanced ratio of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), this results in continual airway inflammation and airway remodeling. The emerging protective role of a specific group of tissue-resident eosinophils (rEos), long-lived tissue-resident memory CD4⁺ T cells (TRM) and B cells (BRM), resident macrophages, endothelial cell (ECs), and innate lymphoid cells (ILC2) in amelioration of asthma is disclosing the novel approach for attenuation of asthma pathogenesis. This new understanding emphasizes the elasticity, tenacity, and communication of myeloid and lymphoid cells in the lung microenvironment, opening the door to new therapeutic possibilities, particularly for severe and chronic asthma. This review combines recent findings that refine our understanding of how immune cells contribute to asthma development and progression. It highlights the important roles of innate immune cells and tissue-resident memory lymphocytes, their interactions with resident cells, and also identifies new treatment approaches that could attenuate asthma progression.