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Study of Dendritic Cell Development by Short Hairpin RNA-Mediated Gene Knockdown in a Hematopoietic Stem and Progenitor Cell Line In vitro
Published on: March 7, 2022
The signal transducers STAT5 and STAT3 control expression of Id2 and E2-2 during dendritic cell development
Haiyan S Li1, Cliff Y Yang, Kalyan C Nallaparaju
1Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
Cytokines and transcription factors play key roles in dendritic cell (DC) development, yet information about regulatory interactions between these signals remains limited. Here we show that the cytokines GM-CSF and Flt3L induce the transcriptional mediators Id2 and E2-2 and control DC lineage diversification by STAT-dependent pathways. We found that STAT5 is required for tissue CD103(+) DC generation and plasmacytoid DC (pDC) suppression in steady state or response to GM-CSF. STAT5 stimulates GM-CSF-dependent expression of Id2, which controls CD103(+) DC production and pDC inhibition. By contrast, pDCs, but not CD103(+) DCs, are dependent on STAT3. Consistently, STAT3 stimulates Flt3L-responsive expression of the pDC regulator Tcf4 (E2-2). These data suggest that STATs contribute to DC development by controlling transcription factors involved in lineage differentiation.
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