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

Olga Spadaro, Emily L. Goldberg, Christina D. Camell, Yun Hee Youm, John J. Kopchick, Kim Y. Nguyen, Andrzej Bartke, Liou Y. Sun, Vishwa Deep Dixit

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1571-1580
Number of pages10
JournalCell reports
Volume14
Issue number7
DOIs
StatePublished - Feb 23 2016

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Laron Syndrome
Inflammasomes
Somatotropin Receptors
Macrophages
Chemical activation
T-cells
Aging of materials
Inflammation
T-Lymphocytes
Immune system
Memory Disorders
Myeloid Cells
Ablation
Immune System
Homeostasis
Down-Regulation
Health
Ligands
Data storage equipment
Sensors

Cite this

Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence. / Spadaro, Olga; Goldberg, Emily L.; Camell, Christina D.; Youm, Yun Hee; Kopchick, John J.; Nguyen, Kim Y.; Bartke, Andrzej; Sun, Liou Y.; Dixit, Vishwa Deep.

In: Cell reports, Vol. 14, No. 7, 23.02.2016, p. 1571-1580.

Research output: Contribution to journalArticle

Spadaro, O, Goldberg, EL, Camell, CD, Youm, YH, Kopchick, JJ, Nguyen, KY, Bartke, A, Sun, LY & Dixit, VD 2016, 'Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence', Cell reports, vol. 14, no. 7, pp. 1571-1580. https://doi.org/10.1016/j.celrep.2016.01.044
Spadaro, Olga ; Goldberg, Emily L. ; Camell, Christina D. ; Youm, Yun Hee ; Kopchick, John J. ; Nguyen, Kim Y. ; Bartke, Andrzej ; Sun, Liou Y. ; Dixit, Vishwa Deep. / Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence. In: Cell reports. 2016 ; Vol. 14, No. 7. pp. 1571-1580.
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