Transforming Growth Factor-β1 Drives Neutrophil Chemokinesis, Not Chemotaxis

Purpose

Idiopathic pulmonary fibrosis (IPF) is a devastating condition that is characterized by dysregulated repair responses to alveolar epithelial damage and progressive remodeling of the lung interstitium. Neutrophils are critical responders to tissue injury, but their role in organ fibrosis pathogenesis remains unclear. Neutrophil numbers are increased in bronchoalveolar spaces of IPF patients, and neutrophil activation markers are elevated in fibrotic lung tissue. However, the key mediators driving neutrophil movement in fibrotic lung diseases are unknown. Transforming growth factor-beta 1 (TGFβ1) is a critical pro-fibrotic cytokine, but its effect on neutrophil movement remains unclear. This mechanistic, exploratory study aimed to determine whether TGFβ1 alters neutrophil migration in a direction-dependent (chemotaxis) or direction-independent (chemokinesis) manner and to assess whether TGFβ1 exposure is accompanied by functional changes consistent with neutrophil priming.