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Introduction and Objectives Idiopathic pulmonary fibrosis (IPF) is characterised by a dysregulated repair response to alveolar epithelial damage. Neutrophils house an array of enzymes critical for repair and remodelling. Neutrophil counts are associated with IPF severity, and neutrophil extracellular traps are observed in fibrotic lung tissue. 1 However, the role of neutrophils in IPF remains unknown. This prospective study aimed to compare the phenotype and movement of circulating neutrophils derived from IPF patients to age-matched control participants.Methods Thirty-five IPF and 19 control participants were recruited. Neutrophil and immature granulocyte counts were measured in venous blood using the Sysmex XN-1000 analyser. Neutrophils were isolated via Percoll density gradient centrifugation and cell surface markers analysed by flow cytometry. Plasma levels of Aα-Val 541, an indirect measure of proteinase 3 activity, were quantified by DELFIA.2 Chemotaxis was measured by real-time microscopy using the Insall chamber assay.Results Peripheral neutrophil counts were greater in IPF patients than controls (4.5x10 9/L versus 3.0x109/L, p<0.001). IPF patients had greater immature granulocyte counts (p<0.01) and a lower percentage of CD10positive (maturity marker) neutrophils than controls (p=0.03). CXCR4 (chemokine receptor) and PD-L1 (co-inhibitory molecule) expression was higher in IPF-derived neutrophils (p<0.05). Plasma Aα-Val541 levels were higher in IPF than control participants (p=0.03). Movement responses to the chemoattractants, IL-8 and fMLP were comparable, but IPF neutrophils moved less directly than controls (p<0.001) on exposure to the pro-fibrotic growth factor, 10 ng/mL transforming growth factor-β1 (TGFβ1) (figure 1).Abstract S167 Figure 1(A) Directness of neutrophil movement upon exposure to 10 ng/mL TGFβ1 assessed using the Insall chamber assay. (B-C) Representative microscopy images displaying tracks (lines) of neutrophil movement in response to TGFβ1 (20X magnification)Conclusions IPF patients appear to have an expanded population of immature neutrophils, suggestive of emergency granulopoiesis. Dysregulated movement of IPF neutrophils in response to TGFβ1 suggests that neutrophil dynamics may be altered within the fibrotic microenvironment. Furthermore, elevated levels of the fibrinogen cleavage epitope, Aα-Val 541, implies increased neutrophil degranulation within the interstitum of IPF patients. Ongoing investigation into the interaction between IPF neutrophils and pro-fibrotic mediators may identify a much-needed novel avenue of therapeutic manipulation.References https://doi.org/10.3389/fimmu.2020.02190https://doi.org/10.1183/23120541.00095-2019