Regulation of NK cell transcriptome by Hif1a and Ahr under hypoxia

NK cells responses can be significantly affected by microenvironmental conditions. In pathological conditions, oxygen concentration in tissues can be reduced, lading to hypoxia. Cells adapt to hypoxia by stabilizing transcription factor HIF-1a that mediates its regulatory functions by modifying gene transcription. In many cells, HIF-1a pathway intersect with the activation of the transcription factor AhR due to shared transcriptional co-activator. Here, we investigated how HIF-1a and AhR regulate murine NK cell transcriptome under hypoxia. Overall design: Trascriptome profiling (RNA-seq) of murine NK cells isolated from spleen of Hif1afl/fl, Ahrfl/fl, Hif1afl/fl Ahrfl/fl or from Ncr1iCreHif1afl/fl, Ncr1iCreAhrfl/fl and Ncr1iCreHif1afl/fl Ahrfl/fl mice, cultured in media supplemented with IL-2 in hypoxia (1% O2) for 7 days