Induced Regulatory T Cells Attenuate Poly I:C‐Triggered Acute Lung Injury by Modulating Cytokine Responses

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI) is characterized by severe pulmonary inflammation and edema and carries a high risk of mortality. This study aimed to evaluate the therapeutic potential of induced regulatory T cells (iTregs) as an early intervention to mitigate ALI using a polyinosinic-polycytidylic acid (poly I:C)-induced murine model. METHODS: C57BL/6 mice were intratracheally administered the synthetic double-stranded RNA (dsRNA) analog poly I:C to induce a hyperinflammatory response, followed by intravenous injection of iTreg 1 h later to target the early phase of injury progression. RESULTS: Analysis of bronchoalveolar lavage fluid (BALF) from poly I:C-treated mice revealed significantly elevated proinflammatory cytokines (interleukin [IL])-6, IL-12, TNF-α, interferon [IFN]-β, and IP-10), decreased anti-inflammatory cytokines (IL-10 and transforming growth factor [TGF-β]), increased infiltration of neutrophils, monocytes, and lymphocytes, and evident alveolar damage with thickened walls and edema. Early iTreg administration effectively reversed these effects by suppressing proinflammatory cytokines, restoring IL-10 levels, reducing immune cell infiltration, and mitigating tissue damage. CONCLUSIONS: These findings demonstrate that iTreg therapy effectively modulates the hyperinflammatory response in ALI and may represent a promising strategy for treating severe inflammatory lung diseases.