期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 14, 页码 -出版社
MDPI
DOI: 10.3390/ijms22147564
关键词
hypoxia; dendritic cell; RNASET2
资金
- MIUR [PRIN 2017NTK4HY_002, PRIN 20177J4E75]
- AIRC [20776]
Hypoxia enhances the expression and secretion of RNASET2 in dendritic cells, which is associated with survival, autophagy, and apoptosis in DCs. The expression of RNASET2 under hypoxia is regulated by the PI3K/AKT pathway.
Hypoxia is a key component of the tumor microenvironment (TME) and promotes not only tumor growth and metastasis, but also negatively affects infiltrating immune cells by impairing host immunity. Dendritic cells (DCs) are the most potent antigen-presenting cells and their biology is weakened in the TME in many ways, including the modulation of their viability. RNASET2 belongs to the T2 family of extracellular ribonucleases and, besides its nuclease activity, it exerts many additional functions. Indeed, RNASET2 is involved in several human pathologies, including cancer, and it is functionally relevant in the TME. RNASET2 functions are not restricted to cancer cells and its expression could be relevant also in other cell types which are important players in the TME, including DCs. Therefore, this study aimed to unravel the effect of hypoxia (2% O-2) on the expression of RNASET2 in DCs. Here, we showed that hypoxia enhanced the expression and secretion of RNASET2 in human monocyte-derived DCs. This paralleled the HIF-1 alpha accumulation and HIF-dependent and -independent signaling, which are associated with DCs' survival/autophagy/apoptosis. RNASET2 expression, under hypoxia, was regulated by the PI3K/AKT pathway and was almost completely abolished by TLR4 ligand, LPS. Taken together, these results highlight how hypoxia- dependent and -independent pathways shape RNASET2 expression in DCs, with new perspectives on its implication for TME and, therefore, in anti-tumor immunity.
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