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New article in Cell Reports: How Th2 cells control obesity

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. Kevin Englebert and colleagues from the group of Guillaume Oldenhove 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.

Highlights:
• CD27 upregulates PD-1 expression on fat-resident Th2 cells in an intrinsic manner
• PD-1 shifts the fate of Th2 toward activation-induced cell death
• CD27 deletion results in increased adaptive type 2 immunity in the adipose tissue
• The adaptive axis of type 2 immunity protects against obesity and associated disorders

link to the full manuscript: The CD27/CD70 pathway negatively regulates visceral adipose tissue resident Th2 cells and controls metabolic homeostasis
March 13th 2024 - 17:53