The CXCL13 hub in obesity-related metabolic inflammation: regulation of spatiotemporal heterogeneity and targeted strategies.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

C-X-C motif chemokine ligand 13 (CXCL13) is a crucial regulator of lymphoid tissue development and immune function. It orchestrates homeostasis in secondary lymphoid organs, inflammatory responses in tertiary lymphoid structures (TLSs), and immunometabolic balance within fat-associated lymphoid clusters (FALCs) by mediating the homing of CXCR5+ cells and activating stromal cells. In the context of obesity-related metabolic inflammation, CXCL13 acts as a central hub of immunometabolic dysregulation, driving pathological processes across multiple organs with significant organ- and stage-specific heterogeneity, which reflects spatiotemporal heterogeneity. It mediates the pathological transformation of FALCs in adipose tissue, inducing insulin resistance; promotes TLS formation within pancreatic islets, accelerating β-cell destruction; dynamically regulates atherosclerotic plaque stability in the blood vessels; and undergoes a functional shift from compensatory suppression to profibrotic and procarcinogenic roles during the progression of liver disease. The effects of CXCL13 are highly dependent on the local microenvironment, exhibiting both pro-inflammatory and repair-suppressive effects in diabetic complications. Although targeted therapies show experimental promise, the context-dependent functions of CXCL13 - encompassing both physiological protection and pathological disruption

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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