TACI-Deficient Macrophages Protect Mice Against Metaflammation and Obesity-Induced Dysregulation of Glucose...

Area of Science:

• Immunology
• Metabolic disease research
• Adipose tissue biology

Background:

• Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor involved with TNF superfamily cytokines.
• Obesity and metabolic dysregulation are significant health concerns linked to chronic inflammation.

Purpose of the Study:

• To investigate the role of TACI in diet-induced metabolic changes.
• To identify the immune mechanisms underlying protection from obesity-associated metabolic dysfunction in TACI-deficient mice.

Main Methods:

• Utilized TACI-deficient mice subjected to a high-fat diet (HFD).
• Analyzed immune cell populations in visceral adipose tissue (VAT).
• Performed adoptive transfer of TACI-deficient macrophages and assessed metabolic parameters and immune cell infiltration in recipient mice.

Main Results:

• TACI-deficient mice were protected from HFD-induced weight gain and glucose homeostasis disruption.
• Protection was associated with increased M2 macrophages, eosinophils, and type 2 innate lymphoid cells in VAT, not TACI-mediated adipogenesis.
• Adoptive transfer of TACI-deficient macrophages improved glucose metabolism in obese hosts by recruiting host M2 macrophages and eosinophils to VAT.
• TACI-deficient macrophages secreted IL-10, which maintained adipocyte insulin sensitivity.

Conclusions:

• TACI deficiency confers protection against diet-induced obesity and metabolic dysfunction.
• Immune cell infiltration, particularly M2 macrophages and eosinophils in VAT, mediated by TACI-deficient macrophages, is crucial for metabolic health.
• TACI-deficient macrophages play a protective role against metaflammation and glucose dysregulation via IL-10 secretion.