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ORIGINAL RESEARCH article

Front. Immunol.
Sec. NK and Innate Lymphoid Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1490250

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

Provisionally accepted
Natalie Samper Natalie Samper 1Lilja Hardardottir Lilja Hardardottir 2Delphine M Depierreux Delphine M Depierreux 2Soomin Song Soomin Song 1Ayano Nakazawa Ayano Nakazawa 3Ivan Gando Ivan Gando 1Tomoe Y Nakamura Tomoe Y Nakamura 3Andrew Sharkey Andrew Sharkey 2Carla R Nowosad Carla R Nowosad 1Stefan Feske Stefan Feske 1Francesco Colucci Francesco Colucci 2William A Coetzee William A Coetzee 1*
  • 1 Grossman School of Medicine, New York University, New York, New York, United States
  • 2 University of Cambridge, Cambridge, England, United Kingdom
  • 3 Wakayama University, Wakayama, Wakayama, Japan

The final, formatted version of the article will be published soon.

    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 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 of Kcnj8. Indeed, we found that mice with NK-cell specific Kcnj8 gene ablation have fewer CD11b + CD27 -and KLRG-1 + NK cells in the bone barrow and spleen. These results show that the KATP subunit Kir6.1 has a key role in NK-cell development.

    Keywords: Innate immunity, NK cells, Ion channels, Potassium channels, ATP-sensitive Potassium Channels, NK Cell Maturity KATP channels, KCNJ8, Kir6.1 Potassium channel, Immunity, NK cells

    Received: 02 Sep 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Samper, Hardardottir, Depierreux, Song, Nakazawa, Gando, Nakamura, Sharkey, Nowosad, Feske, Colucci and Coetzee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: William A Coetzee, Grossman School of Medicine, New York University, New York, 10016, New York, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.