Treatment of bleomycin-injured Twist1 FL animals with the CXCR4 blocker AMD3100 decreased the enhanced pulmonary fibrosis associated with the loss of Twist1 and significantly reduced the accumulation of T cells to the lung. Twist1 FL mice were injured with bleomycin or saline control and then treated with or without the CXCR4 blocker AMD3100. Animals were sacrificed on day 14. (A) H&E staining and Masson trichrome staining of lung sections (inset scale bars, 200 μm; original magnification, ×200). (B) The left lungs were processed for collagen determination by the Sircol assay (*p < 0.0001, uninjured versus bleomycin, n = 8–9 and **p = 0.0004 by ANOVA, bleomycin plus vehicle versus bleomycin plus AMD3100, n = 8–9). BAL was processed for flow cytometry for (C) and (D). Dot plots for Ly6G+ neutrophils, CD68+ macrophages, CD3+ T cells, and B220+ B cells from bleomycin-injured Twist1 FL mice treated with or without AMD3100. (E) Ly6G (*p < 0.0001, uninjured plus vehicle versus bleomycin plus vehicle, n = 8–9 and **p < 0.04, bleomycin plus vehicle versus bleomycin plus AMD3100, n = 8–9), (F) CD68 (*p < 0.0001, uninjured plus vehicle versus bleomycin plus vehicle, n = 8–9 and **p < 0.002, bleomycin plus vehicle versus bleomycin plus AMD3100, n = 8–9), (G) CD3 (*p < 0.0001, uninjured plus vehicle versus bleomycin plus vehicle, n = 8–9 and **p < 0.0001, bleomycin plus vehicle versus bleomycin plus AMD3100, n = 8–9), and (H) B220 (*p < 0.0001, uninjured plus vehicle versus bleomycin plus vehicle, n = 8–9). All data were analyzed by ANOVA.