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Cell Rep. 2016 Feb 23;14(7):1571-1580. doi: 10.1016/j.celrep.2016.01.044. Epub 2016 Feb 11.

Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence.

Author information

1
Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520, USA.
2
Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
3
Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62701, USA.
4
Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35203, USA.
5
Section of Comparative Medicine and Program on Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: vishwa.dixit@yale.edu.

Abstract

The hallmarks of age-related immune senescence are chronic inflammation, aberrant expansion of effector memory, and loss of naive T lymphocytes due in part to systemic activation of innate immune sensor NLRP3 inflammasome in myeloid lineage cells. The endogenous mechanisms that regulate inflammasome activation during aging are unknown. Here, we present evidence that growth hormone receptor (GH-R)-dependent downregulation of NLRP3 inflammasome in macrophages is linked to pro-longevity effects that maintain immune system homeostasis in aging. Deletion of GH-R prevented the macrophage-driven age-related activation of inflammasome in response to NLRP3 ligands and also increased the preservation of naive T cells, even in advanced age and with higher IFNγ secretion from effector cells. The mechanism of inflammasome inhibition is linked to autocrine somatotropic axis as ablation of IGF1R in macrophages lowered the NLRP3 inflammasome activation. Together, our findings show that functional somatotropic axis in macrophages controls inflammation, thus linking NLRP3-mediated innate immune signaling to health span and longevity.

PMID:
26876170
PMCID:
PMC5992590
DOI:
10.1016/j.celrep.2016.01.044
[Indexed for MEDLINE]
Free PMC Article

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