Sex hormones gate the neuronal control of dendritic cell migration and immunity
- 11Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA
Abstract
How endocrine states modulate local immune responses is a fundamental question in immunology. Sexual dimorphism is a striking example: females generally mount stronger immune responses than males, yet how sex hormones intersect with local signals is poorly understood. Here, we identify an endocrine-neuro-immune circuit in which sex hormones determine whether immune cells respond to nociceptor signals. In female skin, nociceptor-derived CGRP promotes dendritic cell (DC) migration and T cell priming indirectly through inflammatory monocytes. CGRP induces monocyte production of Activin A, which upregulates CXCR4 on DCs and promotes migration to draining lymph nodes. In males, androgen receptor signaling suppresses monocyte Activin A and silences this circuit. Disrupting the relay abolishes enhanced female immunity, whereas deleting androgen receptor in male monocytes restores neuronal control. Thus, sex hormones regulate immunity by determining how immune cells interpret neuronal signals, revealing how endocrine state can gate local neuroimmune communication to generate sex-specific immune responses.
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BibTeX
@misc{knopper2026hormones,
title = {{Sex hormones gate the neuronal control of dendritic cell migration and immunity}},
author = {K. Knopper and T. L. Ben-Shaanan and J. An and Y. Xu and J. G. Cyster},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.754550},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.754550v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Sex hormones gate the neuronal control of dendritic cell migration and immunity
AU - K. Knopper
AU - T. L. Ben-Shaanan
AU - J. An
AU - Y. Xu
AU - J. G. Cyster
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.754550
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.754550v1
AB - How endocrine states modulate local immune responses is a fundamental question in immunology. Sexual dimorphism is a striking example: females generally mount stronger immune responses than males, yet how sex hormones intersect with local signals is poorly understood. Here, we identify an endocrine-neuro-immune circuit in which sex hormones determine whether immune cells respond to nociceptor signals. In female skin, nociceptor-derived CGRP promotes dendritic cell (DC) migration and T cell priming indirectly through inflammatory monocytes. CGRP induces monocyte production of Activin A, which upregulates CXCR4 on DCs and promotes migration to draining lymph nodes. In males, androgen receptor signaling suppresses monocyte Activin A and silences this circuit. Disrupting the relay abolishes enhanced female immunity, whereas deleting androgen receptor in male monocytes restores neuronal control. Thus, sex hormones regulate immunity by determining how immune cells interpret neuronal signals, revealing how endocrine state can gate local neuroimmune communication to generate sex-specific immune responses.
ER -