Lung CD4+ T-cells in patients with lung fibrosis produce pro-fibrotic interleukin-13 together with interferon-γ
Liv Ingunn Bjoner Sikkeland, Shuo‐Wang Qiao, Thor Ueland, Ole Henrik Myrdal, Łukasz Wyrożemski, Pål Aukrust, Frode L. Jahnsen, Tone Sjåheim, Johny Kongerud, Øyvind Molberg, May Brit Lund, Espen S. Bækkevold
Abstract
Progressive fibrosing interstitial lung diseases (PF-ILD) have poor prognosis and survival, and their\npathogenesis is not well understood[1]. Mechanistically, lung fibrosis is thought to result from\ndistorted wound-healing following tissue insults and inflammation, leading to scar formation by\nexcess deposition of extracellular matrix proteins and destruction of lung architecture[2]. The\nfibrotic process is complex, and CD4+ T cells are likely involved by their production of a wide\nrange of cytokines and growth factors that promote fibroblast proliferation and differentiation,\ncollagen production, and stimulate production of pro-fibrotic mediators by tissue macrophages[3].\nHowever, CD4+ T cells in PF-ILD are poorly characterized. To this end, we performed a detailed\nanalysis of phenotype, cytokine production and clonality of T cells from the lungs [bronchoalveolar\nlavage (BAL)] of PF-ILD patients. We found that BAL from PF-ILD lungs contained high numbers\nof clonally expanded CD4+ T cells that produced an unusual combination of interferon (IFN) and\npro-fibrotic interleukin (IL)-13. Such cells were not found in patient blood or in control BAL\nsamples.