Epithelial Influence on T Cell Responses and Tissue Remodeling After RSV Infection

Abstract

RSV is a major respiratory pathogen for infants and young children and is strongly associated with the development of asthma later in life. RSV primarily infects the respiratory epithelium and thereby triggers epithelial damage, immune activation and airway inflammation. RSV infection alters the immune response by skewing T cell polarization from the protective Th1 response to Th2, Th9 and Th17 phenotypes. This imbalance is associated with chronic inflammation and airway hypersensitivity. Moreover, the epithelium releases cytokines such as IL-33 and TSLP that promote a type 2 immune response and drives allergic airway responses. Emerging evidence implicates that Th9 and Th17 cells are linked to RSV-induced asthma, promoting tissue remodeling and excessive neutrophil recruitment. Together, these immune mechanisms, alongside the structural changes in the airway epithelium, might highlight an important role for the lung epithelium in the development of asthma. This project therefore investigates the influence of airway epithelial cells on naïve CD4+ T cell responses and tissue remodeling after RSV infection. This was done by examining the gene expression of Beas-2B cells after stimulation with Poly I:C, a viral PAMP mimic, or infection with RSV. Secondly, the activation and differentiation of naïve CD4+ T cells was assessed with flow cytometry and qPCR. The results show that the Beas-2B cells can influence CD4+ T cell activation and differentiation through the increased secretion of factors, such as IL-6, after Poly I:C stimulation and RSV infection, which is linked to Th17 polarization and asthma pathogenesis. In addition, CCL5 and TGF-β1 are downregulated upon Poly I:C stimulation, suggesting an impaired immunoregulatory response. Regarding tissue remodeling, TNC and TGM2 are increasingly expressed in the epithelial cells after both Poly I:C stimulation and RSV infection, suggesting epithelial stress and airway remodeling. These findings highlight the role of epithelialimmune interactions in increased airway inflammation and potentially provide the link between early-life RSV infection and the development of asthma