Stat5 Is Required for CD103+ Dendritic Cell and Alveolar Macrophage Development and Protection from Lung Injury.

ABSTRACT: We tested the role of Stat5 in dendritic cell and alveolar macrophage (AM) homeostasis in the lung using CD11c-cre mediated deletion (Cre+5f/f). We show that Stat5 is required for CD103+ dendritic cell and AM development. We found that fetal monocyte maturation into AMs was impaired in Cre+5f/f mice, and we also confirmed impaired AM development of progenitor cells using mixed chimera experiments. In the absence of Stat5 signaling in AMs, mice developed alveolar proteinosis with altered lipid homeostasis. In addition, loss of Stat5 in CD11c+ cells was associated with exaggerated LPS-induced inflammatory responses and vascular leak. In Cre+5f/f mice, there was loss of immune-dampening effects on epithelial cells, a key source of CCL2 that serves to recruit monocytes and macrophages. These findings demonstrate the critical importance of Stat5 signaling in maintaining lung homeostasis, and underscore the importance of resident macrophages in moderating tissue damage and excess inflammation.

SUBMITTER: Eddy WE 

PROVIDER: S-EPMC5624516 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature