Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development

• Published in: Frontiers in immunology 2024-12, Vol.15, p.1490250
• Main Authors: Samper, Natalie, Hardardottir, Lilja, Depierreux, Delphine M, Song, Soomin C, Nakazawa, Ayano, Gando, Ivan, Nakamura, Tomoe Y, Sharkey, Andrew M, Nowosad, Carla R, Feske, Stefan, Colucci, Francesco, Coetzee, William A
• Format: Article
• Language: English
• Subjects: Animals; ATP-sensitive potassium channels; Cell Differentiation; Female; Immunology; innate immunity; ion channels; KATP Channels - genetics; KATP Channels - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; NK cell development; NK cells; potassium channels; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Uterus - immunology; Uterus - metabolism
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1490250

Involved in immunity and reproduction, natural killer (NK) cells offer opportunities to develop new immunotherapies to treat infections and cancer or to alleviate pregnancy complications. Most current strategies use cytokines or antibodies to enhance NK-cell function, but none use ion channel modulators, which are widely used in clinical practice to treat hypertension, diabetes, epilepsy, and other conditions. Little is known about ion channels in NK cells. We show that , which codes for the Kir6.1 subunit of a certain type of ATP-sensitive potassium (K ) channel, is highly expressed in murine splenic and uterine NK cells compared to other K channels previously identified in NK cells. expression is highest in the most mature subset of splenic NK cells (CD27 /CD11b ) and in NKG2A or Ly49C/I educated uterine NK cells. Using patch clamping, we show that a subset of NK cells expresses a current sensitive to the Kir6.1 blocker PNU-37883A. does not participate in NK cell degranulation in response to tumor cells in vitro or rejection of tumor cells , or IFN-γ release. Transcriptomics show that genes previously implicated in NK cell development are amongst those differentially expressed in CD27 /CD11b NK cells deficient for . Indeed, we found that mice with NK-cell specific gene ablation have fewer CD27 /CD11b and KLRG-1 NK cells in the bone barrow and spleen. These results show that the K subunit Kir6.1 has a key role in NK-cell development.