Phenotypic diversity of human adipose tissue-resident NK cells in obesity

Martha E Haugstøyl; Martin Cornillet; Kristina Strand; Natalie Stiglund; Dan Sun; Laurence Lawrence-Archer; Iren D Hjellestad; Christian Busch; Gunnar Mellgren; Niklas K Björkström; Johan Fernø

doi:10.3389/fimmu.2023.1130370

Phenotypic diversity of human adipose tissue-resident NK cells in obesity

Front Immunol. 2023 Feb 22:14:1130370. doi: 10.3389/fimmu.2023.1130370. eCollection 2023.

Authors

Martha E Haugstøyl^{1

2}, Martin Cornillet³, Kristina Strand^{1

2}, Natalie Stiglund³, Dan Sun³, Laurence Lawrence-Archer^{1

2}, Iren D Hjellestad^{1

4}, Christian Busch⁵, Gunnar Mellgren^{1

2}, Niklas K Björkström³, Johan Fernø^{1

2}

Affiliations

¹ Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
² Mohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.
³ Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
⁴ Department of Medicine, Haukeland University Hospital, Bergen, Norway.
⁵ Plastikkirurg1, Bergen, Norway.

Abstract

Natural killer (NK) cells have emerged as key mediators of obesity-related adipose tissue inflammation. However, the phenotype of NK cell subsets residing in human adipose tissue are poorly defined, preventing a detailed understanding of their role in metabolic disorders. In this study, we applied multicolor flow cytometry to characterize CD56^bright and CD56^dim NK cells in blood and adipose tissue depots in individuals with obesity and identified surface proteins enriched on adipose tissue-resident CD56^bright NK cells. Particularly, we found that adipose tissue harbored clusters of tissue-resident CD56^bright NK cells signatured by the expression of CD26, CCR5 and CD63, possibly reflecting an adaptation to the microenvironment. Together, our findings provide broad insights into the identity of NK cells in blood and adipose tissue in relation to obesity.

Keywords: Natural killer (NK) cell; adipose tissue inflammation; insulin resistance; multicolor flow cytometry; obesity; tissue residency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue* / metabolism
CD56 Antigen / metabolism
Humans
Killer Cells, Natural* / metabolism
Obesity / metabolism
Phenotype

Substances

CD56 Antigen

Grants and funding

This work was funded by the Western Norway Regional Health Authority (Helse Vest RHF), Swedish Research Council, the Swedish Cancer Society, the Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, the Center for Innovative Medicine at Karolinska Institutet, the Stockholm County Council, Karolinska Institutet, Trond Mohn Stiftelse, and The Norwegian Diabetes Association.