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Invariant natural killer T cells and incidence of first-time coronary events : a nested case-control study

Tomas, Lukas LU ; Katra, Pernilla LU ; Badn, Wiaam LU ; Andersson, Linda LU ; Nilsson, Jan LU ; Schiopu, Alexandru LU ; Engelbertsen, Daniel LU ; Gonçalves, Isabel LU orcid ; Bengtsson, Eva LU orcid and Björkbacka, Harry LU orcid (2023) In European Heart Journal Open 3(6).
Abstract

Aims Invariant natural killer T (iNKT) cells, a T cell subset that is CD1d-restricted and expresses a semi-invariant T cell receptor, have been proposed to contribute to dyslipidaemia-driven cardiovascular disease due to their ability to specifically recognize lipid antigens. Studies in mice have attributed pro-atherogenic properties to iNKT cells, but studies in humans investigating associations of iNKT cells with incident coronary events (CE) are lacking. Methods and results Here, we used flow cytometry to enumerate circulating iNKT cells (CD3 CD1d-PBS57-Tetramer) in a case-control cohort nested within the prospective population-based Malmö Diet and Cancer Study (n = 416) to explore associations with incident first-time CE during a... (More)

Aims Invariant natural killer T (iNKT) cells, a T cell subset that is CD1d-restricted and expresses a semi-invariant T cell receptor, have been proposed to contribute to dyslipidaemia-driven cardiovascular disease due to their ability to specifically recognize lipid antigens. Studies in mice have attributed pro-atherogenic properties to iNKT cells, but studies in humans investigating associations of iNKT cells with incident coronary events (CE) are lacking. Methods and results Here, we used flow cytometry to enumerate circulating iNKT cells (CD3 CD1d-PBS57-Tetramer) in a case-control cohort nested within the prospective population-based Malmö Diet and Cancer Study (n = 416) to explore associations with incident first-time CE during a median follow-up of 14 years. We found a significant inverse association between CD4− and CD8− double negative (DN) iNKT cells and incident CE, with an odds ratio of 0.62 [95% confidence interval (CI) 0.38–0.99; P = 0.046] comparing the highest vs. the lowest tertile of DN iNKT cells. The association remained significant after adjustment for cardiovascular risk factors with an odds ratio of 0.57 (95% CI 0.33–0.99; P = 0.046). In contrast, total iNKT cells were not significantly associated with incident CE after adjustment with an odds ratio of 0.74 (95% CI 0.43–1.27; P = 0.276). Conclusion Our findings indicate that animal studies suggesting an atherosclerosis-promoting role for iNKT cells may not translate to human cardiovascular disease as our data show an association between high circulating numbers of DN iNKT cells and decreased risk of incident CE.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Case-control study, Coronary artery disease, Inflammation, Invariant natural killer T cells, Lymphocytes, Prospective study
in
European Heart Journal Open
volume
3
issue
6
article number
oead094
publisher
Oxford University Press
external identifiers
  • pmid:38025652
  • scopus:85178017281
ISSN
2752-4191
DOI
10.1093/ehjopen/oead094
language
English
LU publication?
yes
id
2509ea4f-cc7d-4283-8dc3-0540cece826a
date added to LUP
2024-01-04 16:54:19
date last changed
2024-04-19 13:13:59
@article{2509ea4f-cc7d-4283-8dc3-0540cece826a,
  abstract     = {{<p>Aims Invariant natural killer T (iNKT) cells, a T cell subset that is CD1d-restricted and expresses a semi-invariant T cell receptor, have been proposed to contribute to dyslipidaemia-driven cardiovascular disease due to their ability to specifically recognize lipid antigens. Studies in mice have attributed pro-atherogenic properties to iNKT cells, but studies in humans investigating associations of iNKT cells with incident coronary events (CE) are lacking. Methods and results Here, we used flow cytometry to enumerate circulating iNKT cells (CD3 CD1d-PBS57-Tetramer) in a case-control cohort nested within the prospective population-based Malmö Diet and Cancer Study (n = 416) to explore associations with incident first-time CE during a median follow-up of 14 years. We found a significant inverse association between CD4<sup>−</sup> and CD8<sup>−</sup> double negative (DN) iNKT cells and incident CE, with an odds ratio of 0.62 [95% confidence interval (CI) 0.38–0.99; P = 0.046] comparing the highest vs. the lowest tertile of DN iNKT cells. The association remained significant after adjustment for cardiovascular risk factors with an odds ratio of 0.57 (95% CI 0.33–0.99; P = 0.046). In contrast, total iNKT cells were not significantly associated with incident CE after adjustment with an odds ratio of 0.74 (95% CI 0.43–1.27; P = 0.276). Conclusion Our findings indicate that animal studies suggesting an atherosclerosis-promoting role for iNKT cells may not translate to human cardiovascular disease as our data show an association between high circulating numbers of DN iNKT cells and decreased risk of incident CE.</p>}},
  author       = {{Tomas, Lukas and Katra, Pernilla and Badn, Wiaam and Andersson, Linda and Nilsson, Jan and Schiopu, Alexandru and Engelbertsen, Daniel and Gonçalves, Isabel and Bengtsson, Eva and Björkbacka, Harry}},
  issn         = {{2752-4191}},
  keywords     = {{Case-control study; Coronary artery disease; Inflammation; Invariant natural killer T cells; Lymphocytes; Prospective study}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{6}},
  publisher    = {{Oxford University Press}},
  series       = {{European Heart Journal Open}},
  title        = {{Invariant natural killer T cells and incidence of first-time coronary events : a nested case-control study}},
  url          = {{http://dx.doi.org/10.1093/ehjopen/oead094}},
  doi          = {{10.1093/ehjopen/oead094}},
  volume       = {{3}},
  year         = {{2023}},
}