Adipocyte CD1d Gene Transfer Induces T Cell Expansion and Adipocyte Inflammation in CD1d Knockout Mice

Area of Science:

• Immunology
• Metabolic Disease
• Cell Biology

Background:

• CD1d is a lipid-presenting molecule crucial for invariant NKT (iNKT) cell function and adipose tissue homeostasis.
• Understanding adipocyte-immune cell interactions is vital for metabolic health.

Purpose of the Study:

• To investigate the role of adipocyte CD1d in regulating adipose tissue immunity and function.
• To elucidate the mechanisms by which CD1d influences immune cell populations within adipose tissue.

Main Methods:

• Developed an adipocyte-specific adeno-associated viral vector for CD1d gene delivery in CD1d knockout mice.
• Assessed immune cell alterations, adipocyte gene expression, and inflammasome activation.
• Utilized NLRP3 inhibitors and CD8+ T cell depletion for mechanistic studies.

Main Results:

• Adipocyte CD1d restoration failed to rescue iNKT cells but caused selective expansion of CD8+ T cells.
• This expansion correlated with NLRP3 inflammasome activation, dysregulated adipocyte genes, and apoptosis.
• CD8+ T cell depletion ameliorated inflammasome activation and adipocyte gene dysregulation.

Conclusions:

• Uncovered a novel adipocyte CD1d → CD8+ T cell → adipocyte inflammasome cascade.
• CD8+ T cells act as key mediators of adipocyte inflammation, potentially via an allogeneic response to CD1d.
• This pathway offers new insights into adipose tissue inflammation and metabolic dysfunction.