18β-glycyrrhetinic acid breaks the growth-immunity trade-off via selective suppression of adaptive immunity
- 1State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture & Beijing Key Laboratory for Animal Genetic Improvement, China Agricultural University
- 2Institute of Animal Science, Ningxia Academy of Agriculture and Forestry Sciences
- 3Gansu Agricultural University
Abstract
Background: While the growth-immunity trade-off has been extensively studied in plant biology, its existence, underlying immunometabolic mechanisms, and practical implications in animals remain poorly characterized. Chronic immune activation diverts essential bioenergetic resources away from somatic development, highlighting a critical need for interventions capable of modulating this physiological balance. The potent anti-inflammatory properties of 18β-glycyrrhetinic acid (GA), an active component of licorice, provide a unique opportunity to elucidate this regulatory mechanism.
Methods: To elucidate the regulatory logic of this trade-off in ruminants, we integrated large-scale physiological profiling, multi-tissue bulk transcriptomics, single-cell RNA sequencing (scRNA-seq), limited proteolysis-coupled mass spectrometry (LiP-MS), and molecular docking. We evaluated a large lamb cohort (n = 448) to determine the systemic and molecular effects of maternal 18β-glycyrrhetinic acid (GA) supplementation on offspring.
Results: Gestational GA administration significantly dampened systemic inflammatory tone and oxidative stress, redirecting metabolic resources to somatic growth. This resulted in marked improvements in offspring birth weight (by 7.09%), weaning weight (by 10.66%), skeletal muscle fiber development, and secondary hair follicle maturation. Inter-tissue communication analysis pinpointed the lymph node as the primary signaling hub for GA-mediated inter-organ regulation. Specifically, scRNA-seq revealed that GA preferentially acts on adaptive T-cell subpopulations within the lymph nodes. Furthermore, LiP-MS and molecular docking identified key NF-κB pathway components—specifically PARP1, DDX1, RIPK1, HSPA1A, FLOT1, FLNA, REL, and TRADD—as direct physical binding targets of GA. By engaging these molecular targets, GA suppresses hyperactivated NF-κB signaling in T cells, reducing pro-inflammatory cytokine production and the bioenergetic costs of immune maintenance.
Conclusion: This study establishes the operational animal growth-immunity trade-off paradigm and demonstrates that maternal GA intervention successfully optimizes livestock growth performance and systemic homeostasis through precise immunometabolic regulation.
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BibTeX
@article{wang202618βglycyrrhetinic,
title = {{18β-glycyrrhetinic acid breaks the growth-immunity trade-off via selective suppression of adaptive immunity}},
author = {Yixian Wang and Ruili Liu and Zhengwei Zhao and Jin Wang and Jueying Liu and Jiajie Yao and Letian Zhang and Hongyang Zhao and Lina Ma and Qing Ma and Xuemei Deng and Jiankui Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1995438},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1995438/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 18β-glycyrrhetinic acid breaks the growth-immunity trade-off via selective suppression of adaptive immunity
AU - Yixian Wang
AU - Ruili Liu
AU - Zhengwei Zhao
AU - Jin Wang
AU - Jueying Liu
AU - Jiajie Yao
AU - Letian Zhang
AU - Hongyang Zhao
AU - Lina Ma
AU - Qing Ma
AU - Xuemei Deng
AU - Jiankui Wang
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1995438
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1995438/full
AB - Background: While the growth-immunity trade-off has been extensively studied in plant biology, its existence, underlying immunometabolic mechanisms, and practical implications in animals remain poorly characterized. Chronic immune activation diverts essential bioenergetic resources away from somatic development, highlighting a critical need for interventions capable of modulating this physiological balance. The potent anti-inflammatory properties of 18β-glycyrrhetinic acid (GA), an active component of licorice, provide a unique opportunity to elucidate this regulatory mechanism. Methods: To elucidate the regulatory logic of this trade-off in ruminants, we integrated large-scale physiological profiling, multi-tissue bulk transcriptomics, single-cell RNA sequencing (scRNA-seq), limited proteolysis-coupled mass spectrometry (LiP-MS), and molecular docking. We evaluated a large lamb cohort (n = 448) to determine the systemic and molecular effects of maternal 18β-glycyrrhetinic acid (GA) supplementation on offspring. Results: Gestational GA administration significantly dampened systemic inflammatory tone and oxidative stress, redirecting metabolic resources to somatic growth. This resulted in marked improvements in offspring birth weight (by 7.09%), weaning weight (by 10.66%), skeletal muscle fiber development, and secondary hair follicle maturation. Inter-tissue communication analysis pinpointed the lymph node as the primary signaling hub for GA-mediated inter-organ regulation. Specifically, scRNA-seq revealed that GA preferentially acts on adaptive T-cell subpopulations within the lymph nodes. Furthermore, LiP-MS and molecular docking identified key NF-κB pathway components—specifically PARP1, DDX1, RIPK1, HSPA1A, FLOT1, FLNA, REL, and TRADD—as direct physical binding targets of GA. By engaging these molecular targets, GA suppresses hyperactivated NF-κB signaling in T cells, reducing pro-inflammatory cytokine production and the bioenergetic costs of immune maintenance. Conclusion: This study establishes the operational animal growth-immunity trade-off paradigm and demonstrates that maternal GA intervention successfully optimizes livestock growth performance and systemic homeostasis through precise immunometabolic regulation.
SN - 1664-3224
ER -