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ORIGINAL RESEARCH article

Front. Immunol.

Sec. NK and Innate Lymphoid Cell Biology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1651054

Peripheral blood iNKT cells display an activated profile with both increased apoptosis and dysfunction in obesity

Provisionally accepted
Chloé  WilkinChloé Wilkin1Nathalie  EsserNathalie Esser2Cédric  LassenceCédric Lassence1Marion  BruneteauxMarion Bruneteaux1Marjorie  FadeurMarjorie Fadeur2Jenny  De FlinesJenny De Flines2Nicolas  PaquotNicolas Paquot2Jacques  PietteJacques Piette1Sylvie  Legrand-PoelsSylvie Legrand-Poels1*
  • 1Universite de Liege GIGA Institute, Liège, Belgium
  • 2Centre Hospitalier Universitaire de Liege, Liège, Belgium

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

Abstract. Obesity is characterized by a chronic low-grade inflammation and, paradoxically, is also associated with immune cells dysfunction. In this study, we analysed peripheral blood Invariant Natural killer T cells (iNKT) in individuals with or without obesity. These unconventional T cells recognize lipid antigens presented by the monomorphic CD1d MHC I-like protein. We demonstrated an activation of iNKT cells in individuals with obesity associated with both increased apoptosis and dysfunction as assessed by the lack of responsiveness to PMA/Ionomycin stimulation. This disruption mainly affects the CD4⁻ subset, more dedicated to pro-inflammatory cytokines release and cytotoxicity. Such impact could therefore be involved in the loss of immunosurveillance observed in obesity. Interestingly, CD1d is upregulated on intermediate and non-classical monocytes from individuals with obesity and its expression on both monocyte subsets is correlated with iNKT cell dysfunction. Both the activation and hypo-responsiveness of iNKT cells as well as CD1d modulation on monocytes are significantly reversed after bariatric surgery. Altogether, these data suggest that increased CD1d expression may enhance the presentation of endogenous lipid antigens, thereby contributing to iNKT cell activation in the context of obesity.

Keywords: iNKT, Obesity, lipid antigens, Monocytes, Activation markers, Cytokines, CD1d

Received: 20 Jun 2025; Accepted: 21 Aug 2025.

Copyright: © 2025 Wilkin, Esser, Lassence, Bruneteaux, Fadeur, De Flines, Paquot, Piette and Legrand-Poels. 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: Sylvie Legrand-Poels, Universite de Liege GIGA Institute, Liège, Belgium

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