Lymph node sterol metabolite drives chemokine-independent lymphocyte trafficking for immune activation

Naïve lymphocytes trafficking from blood to draining lymph nodes (dLNs) is essential for establishing effective immune defense and surveillance, which is primarily mediated by CCL21-CCR7 axis. However, CCL21 is paradoxically suppressed during pathogen invading or tumor progression. Whether and how the lymphocytes are recruited to dLNs for mediating host defense via a previously unknown manner remain to be discovered. A recent study reveals that high-endothelial venules and Langerhans cells in dLNs produce oxysterols, which serve as compensatory chemoattractants to recruit naïve lymphocytes for immune activation. These findings unveil a fundamental paradigm shift in lymphocyte trafficking from chemokine-dependent to sterol metabolite-mediated recruitment, and underscore the therapeutic potential of targeting metabolic reprogramming in empowering lymphocyte trafficking for immune responses against infection and cancer.