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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 \u03b2-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 \u2013 encompassing both physiological protection and pathological disruption \u2013 along with its organ and stage specificity, necessitate spatiotemporally precise interventions. This review systematically elucidates the pivotal role of CXCL13 in obesity-related metabolic inflammation, providing a theoretical foundation for the development of precision intervention strategies tailored to disease subtypes, stages, and specific organ targeting.<\/jats:p>","DOI":"10.1530\/joe-25-0295","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:13:23Z","timestamp":1774527203000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":0,"title":["The CXCL13 hub in obesity-related metabolic inflammation: regulation of spatiotemporal heterogeneity and targeted 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