Roles for STAT5 in homeostasis and function of CD103+cDC1s in non-lymphoid organs

Abstract

Abstract Type 1 conventional dendritic cells (cDC1s) have critical roles in inducing adaptive immune responses and mediating immune tolerance. Signal Transducer and Activator of Transcription 5 (STAT5) was found to be crucial for monocyte-derived DC development; however, its role in non-lymphoid tissue CD103+cDC1s remained largely unknown. We evaluated the role of STAT5 by employing myeloid-specific Stat5-deficient mice,LysM-Cre +Stat5f/f and CD11c-Cre+Stat5f/f mice. Both strains show deficiencies in the numbers of CD103+cDC1s and alveolar macrophages (AMs) in lung, suggesting ineffective maintenance of lung homeostasis. Consistent with this concept, CD11c-Cre+Stat5f/f mice show granulocyte and monocyte accumulation in lung, accompanied by a reduction in the number of CD4+T, CD8+T, and B cells. Moreover, CD11c-Cre+Stat5-deficient mice have increased numbers of alveolar histiocytes, which are also enlarged, as well as accumulation of amorphous and eosinophilic material in alveolar spaces, alveolar histiocytosis, and proteinosis. In addition to the lung, liver CD103+cDC1s were also decreased by Stat5 depletion, however colon CD103+cDC1s were not affected. To examine cell-autonomous roles for STAT5, we generated Stat5-deficient CD103+cDC1s using our established bone marrow culture system, and tested in vitro-differentiated CD103+cDC1s for antigen presentation activity. These assays suggest Stat5 deficiency impaired CD103+cDC1s antigen cross-presentation ability. Taken together, our study showed that STAT5 is required for homeostasis and function of CD103+cDC1s in non-lymphoid organs.