Lung-resident lymphocytes and their roles in respiratory infections and chronic respiratory diseases

Recent scientific breakthroughs have blurred traditional boundaries between innate and adaptive immunity, revealing a sophisticated network of tissue-resident cells that deliver immediate, localized immune responses. These lymphocytes not only provide rapid frontline defense but also present a paradoxical role in the pathogenesis of respiratory diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and the long-term tissue consequences of viral infections including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This review traverses the intricate landscape of lung-resident lymphocytes, delving into their origins, diverse functions, and their dualistic impact on pulmonary health. We dissect their interactions with the microenvironment and the regulatory mechanisms guiding their activity, with an emphasis on their contribution to both immune protection and immunopathology. This review aims to elucidate the complex narrative of these cells, enhancing our understanding of the development of precise therapeutic strategies to combat acute and chronic pulmonary diseases. Through this exploration, the review aspires to shed light on the potential of harnessing lung-resident lymphocytes for the treatment of respiratory conditions.