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We thank Dr Brodlie and coworkers for their letter1 and fully agree on the necessity to evaluate whether cells other than lymphocytes and macrophages are involved in IL-17 release in sarcoid lungs. The main manifestation of sarcoidosis is an accumulation of mononuclear inflammatory cells, mostly CD4+ T cells and monocytes/macrophages in involved organs, including the lungs.2 As specified in our ‘Materials and methods’ section, we evaluated cells obtained by filtering bronchoalveolar lavage (BAL) fluid through gauze. A standard morphological and immunological analysis of BAL cellular components was performed. The analysis included cell recovery and differential count of macrophages, lymphocytes, neutrophils and eosinophils (table 1) coupled with a flow cytometry analysis of BAL cells.
Table 1 integrates information given in our published paper,2 clearly demonstrating that the number of BAL neutrophils was fair in our case series. This unfortunately prevented a definitive evaluation of whether polymorph nucleates represent a source of IL-17. Nonetheless, as shown in figure 1, in selected cases with a significant number of BAL neutrophils (two subjects) a certain degree of IL-17 expression was shown. Experiments are in progress in our lab aimed at evaluating the role of the IL-17 and neutrophil interaction in fibrogenic diffuse parenchymal lung disease (DPLD), including sarcoidosis. In fact, neutrophils are known to play a crucial role in alveolar injury mechanisms in idiopathic pulmonary fibrosis and other types of DPLD. Furthermore, it has recently been shown that Th17 cells and IL-17A favour the development of fibrosis in a murine model of bleomycin-induced pulmonary fibrosis.3 Finally, patients with idiopathic pulmonary fibrosis show high BAL levels of IL-17.3
Concerning putative mechanism through which IL-17 could in theory regulate neutrophil activation and recruitment, we are evaluating whether pulmonary IL-17 favours granulopoiesis in DPLD (via granulocyte colony stimulating factor or granulocyte-macrophage colony stimulating factor)4 5 and induces neutrophil chemotaxis through stimulation of endothelial and epithelial cells. Nonetheless, it is important to note that IL-17 also has the capability of mediating neutrophil apoptosis and neutrophil phagocytosis through macrophages.6 Thus, since IL-17 regulates both recruitment and turnover of neutrophils, we are assessing whether lung IL-17 upmodulates or downmodulates neutrophils during the different phases of DPLD, including sarcoidosis.
Competing interests None.
Ethics approval This study was conducted with the approval of the Padua Ethics Committee.
Provenance and peer review Not commissioned; not externally peer reviewed.
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