The role of TGF-β in the differentiation and lung specification of murine type 1 conventional dendritic cells.

Abstract Lung-resident type 1 conventional dendritic cells (cDC1s) are critical for initiating immune responses against foreign respiratory viruses and endogenous assaults like cancer cells. Importantly, the cDCs of each tissue display unique phenotypes functions dictated by environment they populate. However, our understanding factors that regulate cDC1 development function in lung is minimal. The cytokines, FMS-like tyrosine kinase 3 ligand (FLT3L), granulocyte-macrophage stimulating factor (GM-CSF) essential tissue-resident cDC1, but vitro systems, these insufficient to generate cDC1s with a lung-specific phenotype. RNAseq analysis identified clear enrichment genes associated transforming growth beta (TGF-β) signaling, also known be enriched airspaces lung. TGF-β has been previously reported maintain DC quiescence lung, however, data suggested it may play role differentiation specification Based on this, I hypothesized adding bone marrow (BM) cultures alongside established cytokines FLT3L GM-CSF would phenotypically functionally similar vivo cDC1s. addition TGF-β, not GM-CSF, optimized FLT3L-BMDC resulted which highly resemble cDC1. high throughput system differentiates functional will only inform required provides useful platform interrogation stepping-off point begin models human production study Supported grants from University Washington PREP program NIH (R25) Fred Hutchinson Cancer Center Diversity, Equity, Inclusion Student Fellowship