2. Academic Validation
  3. Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity

Innervation of nociceptor neurons in the spleen promotes germinal center responses and humoral immunity

  • Cell. 2024 May 15:S0092-8674(24)00453-7. doi: 10.1016/j.cell.2024.04.027.
Min Wu 1,  Guangping Song 2,  Jianing Li 1,  Zengqing Song 1,  Bing Zhao 1,  Liyun Liang 2,  Wenlong Li 3,  Huaibin Hu 1,  Haiqing Tu 1,  Sen Li 1,  Peiyao Li 2,  Biyu Zhang 1,  Wen Wang 1,  Yu Zhang 4,  Wanpeng Zhang 1,  Weifan Zheng 1,  Jiarong Wang 1,  Yuqi Wen 1,  Kai Wang 1,  Ailing Li 1,  Tao Zhou 5,  Yucheng Zhang 6,  Huiyan Li 7
Affiliations

Affiliations

  • 1 Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, China.
  • 2 Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, China; School of Medicine, Tsinghua University, Beijing, China.
  • 3 Chinese Institute for Brain Research, Beijing, China.
  • 4 School of Basic Medical Sciences, Fudan University, Shanghai, China.
  • 5 Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, China. Electronic address: tzhou@ncba.ac.cn.
  • 6 Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, China. Electronic address: yczhang@xmail.ncba.ac.cn.
  • 7 Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, China. Electronic address: hyli@ncba.ac.cn.
PMID: 38772371 DOI: 10.1016/j.cell.2024.04.027
Abstract

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release Calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.

Keywords

B cells; CGRP; TRPV1; capsaicin; germinal center responses; humoral immunity; neuroimmune crosstalk; nociceptor neurons; spleen.

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