The CD27/CD70 pathway negatively regulates visceral adipose tissue resident Th2 cells and controls metabolic homeostasis

The adipose tissue homeostasis relies on the interplay between several regulatory lineages, such as ILC2, Th2, Treg, eosinophils and type 2 macrophages. Among them, ILC2 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 (TSLP, IL-33) between ILC2 and resident memory Th2 lymphocytes, the role of the adaptive axis of type-2 immunity remains unclear. We show that mice deficient for CD27, a member of the TNF 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 CD27KO mice, which correlated with decreased PD-1-induced apoptosis. Our data point to a non-redundant role for Th2 lymphocytes in obesogenic conditions. C57Bl/6 mice were crossed with CD11c-Cd70tg;CD27-/- or CD27-/- to generate CD11c-Cd70tg;CD27+/- mice and CD27+/- control mice. Stromal vascular fractions of VAT of 10 WT or CD27-/- mice were pooled and TCR+ CD4+ cells were subsequently FACS-sorted. Cells were next loaded on the Chromium Controller (10x Genomics) and single-cell RNA-seq libraries were prepared using the Chromium Single Cell 3′ v3.1 Reagent Kit (10x Genomics) according to manufacturer’s user guide CG000206.