Dysregulated alveolar type 2 epithelial cell proteostasis promotes fibrogenic macrophage migration inhibitory factor–CD74 signaling

) transgenic mouse models and in ex vivo human precision-cut lung slices treated with fibrotic cocktail. In study participants with IPF, BALF MIF was elevated compared with that in study participants without IPF. In participants with IPF, BALF MIF greater than 4000 picograms per milliliter was associated with increased mortality compared with participants with IPF with lower MIF. Together, these findings define a UPS-sensitive epithelial-macrophage signaling connection and identify MIF-CD74 cross-talk as a potential therapeutic target in fibrotic lung disease.