ROLE OF ILCS IN THE PATHOPHYSIOLOGY OF ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

Abstract

Intro: Heightened immune response and cytokine storm are a hallmark of ARDS, manifested due to uncontrollable neutrophil and macrophage activation, thereby provoking inflammatory conditions in the lungs and systemic circulation. Various studies highlighted the potential of innate lymphoid cells (ILCs) in maintaining lung homeostasis under physiological and pathological conditions. In the present study, we thus evaluated the role of ILC subsets in the pathogenesis of ARDS. Methods: For investigating the role of ILCs (ILC1, ILC2, and ILC3) in the pathogenesis of ARDS, we firstly developed a lipopolysaccharide (LPS) induced ARDS mice model. Hematoxylin and eosin (H& E) staining was carried out to assess the immune cell infiltration in the lungs. Evans blue staining was performed for interrogating the vascular integrity of the lungs. To determine the status of the ILCs subtypes in the lung tissues and BALF, flow cytometry was carried out. Lastly, ELISA was performed for detecting the serum cytokines. Findings: Interestingly, histological patterns depict the accumulation of neutrophils and fibrin, foamy macrophages, and intra-alveolar hemorrhage in the ARDS group in comparison to the control group. Further, Evans blue staining revealed the loss of vascular integrity in the lungs. Moreover, our flow cytometry data demonstrated a significant reduction in the percentage of CD3-Tbet+ ILC1 population along with a simultaneous induction in the percentage of CD3-GATA3+ ILC2 and CD3-Roryt+ ILC3 population in the ARDS model as compared to the control group. In consistent to this, serum cytokine data further indicated an increase in inflammatory cytokines and ILCs signature cytokines such as IL- 17, TNF-α, IL-6, etc. Conclusion: Altogether, our study for the first time strongly suggests the inflammatory role of ILC2 and ILC3 in the immunopathogenesis of LPS-induced acute-lung-injury. In addition, the present study demonstrated the vital role of ILCs in regulating vascular integrity along with controlling lung tissue homeostasis under both physiological and pathological conditions.