Lung CD4+ T cells in patients with lung fibrosis produce pro-fibrotic IL-13 together with IFNγ

Abstract

Progressive fibrosing interstitial lung diseases (PF-ILD) have poor prognosis and survival, and their pathogenesis is not well understood[1]. Mechanistically, lung fibrosis is thought to result from distorted wound-healing following tissue insults and inflammation, leading to scar formation by excess deposition of extracellular matrix proteins and destruction of lung architecture[2]. The fibrotic process is complex, and CD4+ T cells are likely involved by their production of a wide range of cytokines and growth factors that promote fibroblast proliferation and differentiation, collagen production, and stimulate production of pro-fibrotic mediators by tissue macrophages[3]. However, CD4+ T cells in PF-ILD are poorly characterized. To this end, we performed a detailed analysis of phenotype, cytokine production and clonality of T cells from the lungs [bronchoalveolar lavage (BAL)] of PF-ILD patients. We found that BAL from PF-ILD lungs contained high numbers of clonally expanded CD4+ T cells that produced an unusual combination of interferon (IFN)  and pro-fibrotic interleukin (IL)-13. Such cells were not found in patient blood or in control BAL samples.