China-Australia Centre for Personalised Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.
Nat Commun. 2021 May 24;12(1):3073. doi: 10.1038/s41467-021-23220-x.
Follicular helper T (T) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate T function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying T regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human T differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs T generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of T cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.
滤泡辅助 T（T）细胞通过支持抗体亲和力成熟和记忆形成来控制抗体反应。在对疫苗反应无效的个体中发现 T 功能不足，但疫苗接种中 T 调节的机制尚不清楚。在这里，我们报告说，代谢激素瘦素的血清水平较低与健康人群对流感或乙型肝炎病毒疫苗的反应降低有关。瘦素通过 STAT3 和 mTOR 途径促进小鼠和人类 T 细胞分化和 IL-21 产生。瘦素受体缺乏会损害免疫接种和感染过程中的 T 细胞生成和抗体反应。同样，禁食引起的瘦素缺乏会降低流感疫苗接种对随后感染挑战的保护作用，而瘦素替代可在很大程度上挽救这种作用。我们的结果将瘦素确定为 T 细胞分化和功能的调节剂，并表明瘦素水平低是疫苗接种失败的一个风险因素。
