Generation of doxycycline (DOX)-regulated IL-15 transgenic mice, and analysis of tissue collagen and profibrotic cytokines in saline- and Aspergillus-exposed CC10–IL-15 bitransgenic mice. (A) Construct of (tetO) 7 CMV-IL15 transgenic mice and rtTA-CC10 transgenic mice to generate rtTA-CC10–IL-15 bitransgenic mice. (B) Induction of IL-15 levels in the lung and BAL fluid (BALF) after 3 weeks of DOX exposure to rtTA-CC10–IL-15 bitransgenic mice. (C) A representative photomicrograph of Masson’s trichrome-stained saline- and Aspergillus-challenged DOX- and no-DOX–exposed CC10–IL-15 bitransgenic mice. (D) Total lung collagen, and the profibrotic cytokines (IL-13 and TGF-β1) in saline and Aspergillus-challenged no-DOX and DOX exposed IL-15 transgenic mice are shown (E and F). Immunofluorescence staining revealed α-SMA+ cells in saline- and Aspergillus-challenged no-DOX– and DOX-exposed IL-15 transgenic mice. (G) Very few α-SMA+ cells are seen in the saline-treated (for 3 wk) mice. (H) Quantitation of α-SMA+ cells in saline- and Aspergillus-challenged IL-15 transgenic mice. (I) Arrows indicated FSP1+ cells detected in Aspergillus-challenged no-Dox– and Dox-exposed IL-15 transgenic mice. (J) Quantitation of FSP1+ cells in saline- and Aspergillus-challenged Dox- and no-Dox–exposed transgenic mice. Data are expressed as mean ± SD, n = 12 mice/group. Scale bars: 20 μm, 50 μm, and 100 μm. bGH = bovine growth hormone; CC10 = CC10-Clara cell 10 kD protein; CMV = cytomegalovirus (promoter); hGH = human growth hormone; rtTA = express a tet repressor-VP16 transcriptional activator fusion gene; TetO7 = tetracycline; Tg = transgenic.