The CD27/CD70 pathway negatively regulates visceral adipose tissue-resident Th2 cells and controls metabolic homeostasis
Kevin Englebert,
Anaelle Taquin,
Abdulkader Azouz,
Valérie Acolty,
Sylvie Vande Velde,
Marie Vanhollebeke,
Hadrien Innes,
Louis Boon,
Tibor Keler,
Oberdan Leo,
Stanislas Goriely,
Muriel Moser,
Guillaume Oldenhove
Affiliations
Kevin Englebert
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium
Anaelle Taquin
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium
Abdulkader Azouz
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Institute for Medical Immunology (IMI), ULB, Gosselies, Belgium
Valérie Acolty
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium
Sylvie Vande Velde
Interuniversity Institute of Bioinformatics in Brussels (ULB-VUB), Brussels, Belgium; Machine Learning Group, ULB, Brussels, Belgium
Marie Vanhollebeke
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium
Hadrien Innes
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium
Louis Boon
JJP Biologics, Warsaw, Poland
Tibor Keler
Celldex Therapeutics, Hampton, NJ, USA
Oberdan Leo
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium
Stanislas Goriely
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium; Institute for Medical Immunology (IMI), ULB, Gosselies, Belgium
Muriel Moser
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium
Guillaume Oldenhove
ULB Center for Research in Immunology (U-CRI), Université Libre de Bruxelles (ULB), Brussels, Belgium; Immunobiology Lab, ULB, Gosselies, Belgium; Corresponding author
Summary: Adipose tissue homeostasis relies on the interplay between several regulatory lineages, such as type 2 innate lymphoid cells (ILC2s), T helper 2 (Th2) cells, regulatory T cells, eosinophils, and type 2 macrophages. Among them, ILC2s are numerically the dominant source of type 2 cytokines and are considered as major regulators of adiposity. Despite the overlap in immune effector molecules and sensitivity to alarmins (thymic stromal lymphopoietin and interleukin-33) between ILC2s and resident memory Th2 lymphocytes, the role of the adaptive axis of type 2 immunity remains unclear. We show that mice deficient in CD27, a member of the tumor necrosis factor receptor superfamily, are more resistant to obesity and associated disorders. A comparative analysis of the CD4 compartment of both strains revealed higher numbers of fat-resident memory Th2 cells in the adipose tissue of CD27 knockout mice, which correlated with decreased programmed cell death protein 1-induced apoptosis. Our data point to a non-redundant role for Th2 lymphocytes in obesogenic conditions.
