| Autor: |
Kyungwoo Lee, Su Hwa Jang, Hong Tian, Sun Jung Kim |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology, Vol 11 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2020.01436 |
| Popis: |
Proper expression of the transcription factor, Positive regulatory domain 1 (PRDM1), is required for maintaining homeostasis of human monocyte derived-dendritic cells (MO-DCs). The molecular mechanisms and gene targets of PRDM1 in B and T lymphocytes have been identified. However, the function of PRDM1 in dendritic cells (DCs) remains unclear. We investigate co-regulators of PRDM1 in MO-DCs identified by mass spectrometry (MS) and co-immunoprecipitation (Co-IP). Notably, non-POU domain-containing octamer-binding protein (NonO) was found to be a PRDM1 binding protein in the nucleus of MO-DCs. NonO is recruited to the PRDM1 binding site in the promoter region of IL-6. Knockdown of NonO expression by siRNA lessened suppression of IL-6 promoter activity by PRMD1 following LPS stimulation. While NonO binding to PRDM1 was observed in human myeloma cell lines, an effect of NonO on IL-6 expression was not observed. Thus, loss of NonO interrupted the inhibitory effect of PRDM1 on IL-6 expression in MO-DCs, but not plasma cells. Moreover, MO-DCs with low expression of PRDM1 or NonO induce an increased number of IL-21-producing TFH-like cells in vitro. These data suggest that low level of PRDM1 and NonO lead to enhanced activation of MO-DCs and the regulation of MO-DC function by PRDM1 is mediated through cell lineage-specific mechanisms. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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