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<p>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&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月4日

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  • Jianru Chen,
  • Xuetao Cao

摘要

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.