Crosstalk between lung fibroblasts and T-lymphocytes: Implications for anti-viral responses in chronic lung disease

Background Increased numbers of CD4+T-cell subpopulations have been identified in many chronic lung diseases associated with fibrotic remodeling, including asthma, COPD and BOS. Whether CD4 cells directly influence or are influenced by immune functions of fibroblast remains unclear. Evaluating the crosstalk between these cells might provide opportunities for new therapeutic approaches to chronic lung disease. Methods CD4 cells were isolated from human peripheral blood and cultured in conditioned media from human lung fibroblasts for 5 days, after which the IL-17, INFg and IL-4 protein expression was measured in CD4 cells by flow cytometry. To assess the influence of CD4 cell-derived cytokines on immune functions of fibroblasts, they were treated with IL-17, IFNg or a combination of IL-4 and IL-13. Expression of IL-6, IL-8 and pattern recognition receptors (PRR) was measured in fibroblasts by qRT-PCR. Results CD4 cells cultured in conditioned media from fibroblasts showed increased expression of IL-17, INFg and IL-4 (p<0.05, n=5) in comparison to CD4 cells cultured in fresh media. IL-17 treatment increased expression of IL-8 and IL-6 in fibroblasts whereas IFNg upregulated expression of MHC2, CD40 and the PRRs, TLR3, RIG1 and MDA5 (p<0.05, n=3). Conclusions Secretory products of lung fibrobalsts have an effect on CD4 cell phenotype and CD4 cell derived cytokines, IL-17 and IFNg trigger pro-inflammatory and innate responses respectively in lung fibroblasts. This suggests that Th1 and Th17 CD4 cells may enhance fibroblast responsiveness to viral infections. Crosstalk between these cell types may be an important mechanism in acute exacerbations of chronic lung diseases.