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.