Autor: |
Kittitach Sri-ngern-ngam, Pornlapat Keawvilai, Trairak Pisitkun, Tanapat Palaga |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
Biochemistry and Biophysics Reports, Vol 32, Iss , Pp 101369- (2022) |
Druh dokumentu: |
article |
ISSN: |
2405-5808 |
DOI: |
10.1016/j.bbrep.2022.101369 |
Popis: |
Programmed cell death 1 (PD-1) is a co-inhibitory checkpoint receptor expressed in various immune cells, especially in activated T cells. Engagement of PD-1 with its ligand leads to the exhausted T cells and impaired antitumor immunity. To date, PD-1 expression and its roles have been widely reported in T cells but not well defined in innate immune cells including monocytes. In this study, expression of PD-1 was investigated in human monocytes. Here we observed that among cytokines tested, IFN-γ significantly upregulated the PD-1 expression in both THP-1 cell line and human primary monocytes in a dose- and time-dependent manner. This effect was reduced by PI3K inhibitor, suggesting that the involvement of PI3K/AKT pathway. Furthermore, enrichment of active histone mark H3K4me3 in the Pdcd1 promotor was also observed in IFN-γ-induced THP-1, indicating that epigenetic regulation also plays a role in IFN-γ-induced PD-1 expression. To investigate the biological functions of PD-1, Pdcd1 was deleted in THP-1 cell line by CRISPR/Cas9 system and the phagocytic ability was investigated. The results showed that the PD-1 deficiency in THP-1 cell line resulted in significantly poor phagocytic potency against carboxylated-modified latex beads. Moreover, the PD-1 deficiency or blocking PD-1/PD-L1 interaction by immune checkpoint inhibitor resulted in an impaired induction of IL-4-induced CD163 expression in THP-1 cell line. Taken together, these results highlighted the importance of PD-1 expression in some of key monocyte functions. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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