Functional TRPA1 Channels Regulate CD56<sup>dim</sup>CD16<sup>+</sup> NK Cell Cytotoxicity against Tumor Cells
Transient receptor potential ankyrin 1 (TRPA1) channels are expressed on the surface of different cell types, including immune cells. However, TRPA1’s role in the context of innate and adaptive immune responses has not been fully elucidated so far. In this study, we aimed at investigating the expres...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/19/14736 |
| _version_ | 1797575777203519488 |
|---|---|
| author | Fernanda Scopelliti Valentina Dimartino Caterina Cattani Andrea Cavani |
| author_facet | Fernanda Scopelliti Valentina Dimartino Caterina Cattani Andrea Cavani |
| author_sort | Fernanda Scopelliti |
| collection | DOAJ |
| description | Transient receptor potential ankyrin 1 (TRPA1) channels are expressed on the surface of different cell types, including immune cells. However, TRPA1’s role in the context of innate and adaptive immune responses has not been fully elucidated so far. In this study, we aimed at investigating the expression and function of TRPA1 channels on NK cells. Among NK cells, TRPA1 was highly expressed by the CD56<sup>dim</sup>CD16<sup>+</sup> subpopulation, but not by CD56<sup>bright</sup>CD16<sup>−</sup> cells, as detected by FACS. TRPA1 activation with the potent ligand allyl isothiocyanate (AITC) induces intracellular calcium flux in CD56<sup>dim</sup>CD16<sup>+</sup> cells, which was prevented by the TRPA1 antagonist HC-030031. AITC treatment increased the membrane around NKp44 and strongly decreased CD16 and CD8 expression, while CD158a, CD159a, NKG2d, NKp46 were substantially unaffected. Importantly, AITC increased the granzyme production and CD107 expression and increased NK cell-mediated cytotoxicity towards the K562 cell line and two different melanoma cell lines. In parallel, TRPA1 activation also plays regulatory roles by affecting the survival of NK cells to limit uncontrolled and prolonged NK cell-mediated cytotoxicity. Our results indicate that the activation of TRPA1 is an important regulatory signal for NK cells, and agonists of TRPA1 could be used to strengthen the tumor response of the immune system. |
| first_indexed | 2024-03-10T21:43:08Z |
| format | Article |
| id | doaj.art-d1d2c95d644b437cb9083e064161a19e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:43:08Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d1d2c95d644b437cb9083e064161a19e2023-11-19T14:30:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191473610.3390/ijms241914736Functional TRPA1 Channels Regulate CD56<sup>dim</sup>CD16<sup>+</sup> NK Cell Cytotoxicity against Tumor CellsFernanda Scopelliti0Valentina Dimartino1Caterina Cattani2Andrea Cavani3National Institute for Health, Migration and Poverty INMP/NIHMP, Via di S.Gallicano, 25, 00153 Rome, ItalyNational Institute for Health, Migration and Poverty INMP/NIHMP, Via di S.Gallicano, 25, 00153 Rome, ItalyNational Institute for Health, Migration and Poverty INMP/NIHMP, Via di S.Gallicano, 25, 00153 Rome, ItalyNational Institute for Health, Migration and Poverty INMP/NIHMP, Via di S.Gallicano, 25, 00153 Rome, ItalyTransient receptor potential ankyrin 1 (TRPA1) channels are expressed on the surface of different cell types, including immune cells. However, TRPA1’s role in the context of innate and adaptive immune responses has not been fully elucidated so far. In this study, we aimed at investigating the expression and function of TRPA1 channels on NK cells. Among NK cells, TRPA1 was highly expressed by the CD56<sup>dim</sup>CD16<sup>+</sup> subpopulation, but not by CD56<sup>bright</sup>CD16<sup>−</sup> cells, as detected by FACS. TRPA1 activation with the potent ligand allyl isothiocyanate (AITC) induces intracellular calcium flux in CD56<sup>dim</sup>CD16<sup>+</sup> cells, which was prevented by the TRPA1 antagonist HC-030031. AITC treatment increased the membrane around NKp44 and strongly decreased CD16 and CD8 expression, while CD158a, CD159a, NKG2d, NKp46 were substantially unaffected. Importantly, AITC increased the granzyme production and CD107 expression and increased NK cell-mediated cytotoxicity towards the K562 cell line and two different melanoma cell lines. In parallel, TRPA1 activation also plays regulatory roles by affecting the survival of NK cells to limit uncontrolled and prolonged NK cell-mediated cytotoxicity. Our results indicate that the activation of TRPA1 is an important regulatory signal for NK cells, and agonists of TRPA1 could be used to strengthen the tumor response of the immune system.https://www.mdpi.com/1422-0067/24/19/14736TRPA1NKimmune systemcalciumcytotoxicity |
| spellingShingle | Fernanda Scopelliti Valentina Dimartino Caterina Cattani Andrea Cavani Functional TRPA1 Channels Regulate CD56<sup>dim</sup>CD16<sup>+</sup> NK Cell Cytotoxicity against Tumor Cells International Journal of Molecular Sciences TRPA1 NK immune system calcium cytotoxicity |
| title | Functional TRPA1 Channels Regulate CD56<sup>dim</sup>CD16<sup>+</sup> NK Cell Cytotoxicity against Tumor Cells |
| title_full | Functional TRPA1 Channels Regulate CD56<sup>dim</sup>CD16<sup>+</sup> NK Cell Cytotoxicity against Tumor Cells |
| title_fullStr | Functional TRPA1 Channels Regulate CD56<sup>dim</sup>CD16<sup>+</sup> NK Cell Cytotoxicity against Tumor Cells |
| title_full_unstemmed | Functional TRPA1 Channels Regulate CD56<sup>dim</sup>CD16<sup>+</sup> NK Cell Cytotoxicity against Tumor Cells |
| title_short | Functional TRPA1 Channels Regulate CD56<sup>dim</sup>CD16<sup>+</sup> NK Cell Cytotoxicity against Tumor Cells |
| title_sort | functional trpa1 channels regulate cd56 sup dim sup cd16 sup sup nk cell cytotoxicity against tumor cells |
| topic | TRPA1 NK immune system calcium cytotoxicity |
| url | https://www.mdpi.com/1422-0067/24/19/14736 |
| work_keys_str_mv | AT fernandascopelliti functionaltrpa1channelsregulatecd56supdimsupcd16supsupnkcellcytotoxicityagainsttumorcells AT valentinadimartino functionaltrpa1channelsregulatecd56supdimsupcd16supsupnkcellcytotoxicityagainsttumorcells AT caterinacattani functionaltrpa1channelsregulatecd56supdimsupcd16supsupnkcellcytotoxicityagainsttumorcells AT andreacavani functionaltrpa1channelsregulatecd56supdimsupcd16supsupnkcellcytotoxicityagainsttumorcells |