{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:54:46Z","timestamp":1776401686837,"version":"3.51.2"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces life-threatening acute lung injury (ALI) and disrupts immune homeostasis, however, the role of epithelial-immune cell crosstalk in driving this pathology remains incompletely elucidated. Respiratory epithelial cells (RECs) as the primary targets of SARS-CoV-2 via the ACE2 receptor, act as central mediators of immune crosstalk that balances antiviral defense and immunopathology in COVID-19. Beyond forming a physical barrier against pathogen invasion, RECs regulate bidirectional crosstalk with immune cells (including alveolar macrophages, dendritic cells, neutrophils, and lymphocytes) through multiple mechanisms, such as cytokine signaling, antigen presentation, PD-L1 checkpoint modulation, and renin-angiotensin-aldosterone system (RAAS) dysregulation. Under physiological conditions, these interactions promote viral clearance and epithelial repair; In contrast, dysregulation of such crosstalk leads to excessive inflammatory responses like cytokine storm and impaires tissue regeneration. Elucidating the molecular dynamics underlying REC-immune crosstalk is crucial for gaining insights into the development of targeted therapies (e.g., modulating cytokine signaling, restoring RAAS balance) to mitigate the severity of COVID-19. This review summarized recent findings to clarify how REC-mediated immune crosstalk dictates antiviral responses and pathological outcomes, thereby providing a theoretical basis for optimizing therapeutic strategies that strengthen antiviral immunity while minimizing immunopathology.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1799580","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:15:27Z","timestamp":1776399327000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Respiratory epithelial cells as central mediators of immune crosstalk in SARS-CoV-2 infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Xingjian","family":"Liu","sequence":"first","affiliation":[{"name":"Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]},{"name":"Chinese Medicine Guangdong Laboratory","place":["Zhuhai, 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