Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development
IntroductionInvolved 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 ch...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490250/full |
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| author | Natalie Samper Lilja Hardardottir Delphine M. Depierreux Soomin C. Song Ayano Nakazawa Ivan Gando Tomoe Y. Nakamura Andrew M. Sharkey Carla R. Nowosad Stefan Feske Francesco Colucci William A. Coetzee William A. Coetzee William A. Coetzee |
| author_facet | Natalie Samper Lilja Hardardottir Delphine M. Depierreux Soomin C. Song Ayano Nakazawa Ivan Gando Tomoe Y. Nakamura Andrew M. Sharkey Carla R. Nowosad Stefan Feske Francesco Colucci William A. Coetzee William A. Coetzee William A. Coetzee |
| author_sort | Natalie Samper |
| collection | DOAJ |
| description | IntroductionInvolved 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. ResultsWe show that Kcnj8, which codes for the Kir6.1 subunit of a certain type of ATP-sensitive potassium (KATP) channel, is highly expressed in murine splenic and uterine NK cells compared to other K+ channels previously identified in NK cells. Kcnj8 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. Kcnj8 does not participate in NK cell degranulation in response to tumor cells in vitro or rejection of tumor cells in vivo, 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 Kcnj8. Indeed, we found that mice with NK-cell specific Kcnj8 gene ablation have fewer CD27-/CD11b+ and KLRG-1+ NK cells in the bone barrow and spleen. DiscussionThese results show that the KATP subunit Kir6.1 has a key role in NK-cell development. |
| format | Article |
| id | doaj-art-6c6109b7f67d40d592753d77bafa8ce3 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-6c6109b7f67d40d592753d77bafa8ce32024-12-02T05:10:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14902501490250Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell developmentNatalie Samper0Lilja Hardardottir1Delphine M. Depierreux2Soomin C. Song3Ayano Nakazawa4Ivan Gando5Tomoe Y. Nakamura6Andrew M. Sharkey7Carla R. Nowosad8Stefan Feske9Francesco Colucci10William A. Coetzee11William A. Coetzee12William A. Coetzee13Department of Pathology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Obstetrics and Gynecology, University of Cambridge, Cambridge, United KingdomDepartment of Obstetrics and Gynecology, University of Cambridge, Cambridge, United KingdomDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Pharmacology, Wakayama Medical University, Wakayama, JapanDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Pharmacology, Wakayama Medical University, Wakayama, JapanDepartment of Pathology, University of Cambridge, Cambridge, United KingdomDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Obstetrics and Gynecology, University of Cambridge, Cambridge, United KingdomDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Neuroscience & Physiology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, United StatesIntroductionInvolved 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. ResultsWe show that Kcnj8, which codes for the Kir6.1 subunit of a certain type of ATP-sensitive potassium (KATP) channel, is highly expressed in murine splenic and uterine NK cells compared to other K+ channels previously identified in NK cells. Kcnj8 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. Kcnj8 does not participate in NK cell degranulation in response to tumor cells in vitro or rejection of tumor cells in vivo, 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 Kcnj8. Indeed, we found that mice with NK-cell specific Kcnj8 gene ablation have fewer CD27-/CD11b+ and KLRG-1+ NK cells in the bone barrow and spleen. DiscussionThese results show that the KATP subunit Kir6.1 has a key role in NK-cell development.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490250/fullinnate immunityNK cellsion channelspotassium channelsATP-sensitive potassium channelsNK cell development |
| spellingShingle | Natalie Samper Lilja Hardardottir Delphine M. Depierreux Soomin C. Song Ayano Nakazawa Ivan Gando Tomoe Y. Nakamura Andrew M. Sharkey Carla R. Nowosad Stefan Feske Francesco Colucci William A. Coetzee William A. Coetzee William A. Coetzee Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development Frontiers in Immunology innate immunity NK cells ion channels potassium channels ATP-sensitive potassium channels NK cell development |
| title | Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development |
| title_full | Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development |
| title_fullStr | Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development |
| title_full_unstemmed | Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development |
| title_short | Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development |
| title_sort | kir6 1 a component of an atp sensitive potassium channel regulates natural killer cell development |
| topic | innate immunity NK cells ion channels potassium channels ATP-sensitive potassium channels NK cell development |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490250/full |
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