Abstract
Abstract STAT4 (Signal Transducer Activator of Transcription factor 4) polymorphisms are risk factors contributed to autoimmune disease. While STAT4 has a dominant role in promoting interferon-gamma (IFN-g) production in T and NK cells, its existence and function exert in human dendritic cells (DCs) are still unknown. To characterize the STAT4 expression in human peripheral DCs, we isolated DCs from buffy coat of health blood donors (n = 4). The ex vivo DCs were enriched and sorted into 3 subtypes including plasmacytoid DCs (pDCs, CD123 +), CD8 +T-cells priming DC (cDC1, CLEC9A +), and CD4 +T-cells priming DC (cDC2/3, CD1c +) through negative selection bead and flow cytometry. The presence of STAT4 as well as its potential target genes (interleukin-12, IL-12 and interleukin-23, IL-23) expression were examined in IFN-beta induced DCs maturation compared to immature DCs, using Real-Time PCR. We found the proportion of DCs subsets in peripheral mononuclear cells which are 0.05%, 0.02% and 0.3% for pDC, cDC1 and cDC2/3, respectively. The IFN-beta enhanced DC maturation markers (HLA-DR +CD86 +), especially in cDC2/3. Interestingly, up-regulated STAT4 expression (2.5-fold) were significantly prominent in mature cDC2/3 compared to immature (p < 0.01), while IFN-beta showed no influence on STAT4 expression in the cDC1 and pDC (p > 0.05). Interestingly, elevated IL-12 and IL-23 expression were significantly observed in activated cDC2/3 (p < 0.05). Further study to investigate the role of STAT4 in human cDC2/3 are needed. Our result firstly discover the existing of STAT4 expression in the ex vivo peripheral human DC. Supported by Chulalongkorn University (Fundamental Fund, CU_FRB65_hea (84)_179_37_09).
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