Journal
JOURNAL OF IMMUNOLOGY
Volume 205, Issue 3, Pages 776-788Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1901330
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Funding
- Spanish Ministry of Science, Innovation and Universities (Agencia Estatal de Investigacion/Fondo Europeo de Desarrollo Regional (AEI/FEDER), Union Europea [UE]) [SAF2017-82940-R]
- Spanish Ministry of Science, Innovation and Universities (AEI/FEDER, UE) [SAF2017-83785-R, FJCI-2016-29990]
- Redes Tematicas de Investigacion Cooperativa en Salud Program of Instituto de Salud Carlos III [RD12/0012/0006, RD12/0012/0007]
- Regional Government of Madrid [B2017/BMD-3804]
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Growth hormone (GH), a pleiotropic hormone secreted by the pituitary gland, regulates immune and inflammatory responses. In this study, we show that GH regulates the phenotypic and functional plasticity of macrophages both in vitro and in vivo. Specifically, GH treatment of GM-CSF-primed monocyte-derived macrophages promotes a significant enrichment of anti-inflammatory genes and dampens the proinflammatory cytokine profile through PI3K-mediated downregulation of activin A and upregulation of MAFB, a critical transcription factor for anti-inflammatory polarization of human macrophages. These in vitro data correlate with improved remission of inflammation and mucosal repair during recovery in the acute dextran sodium sulfate-induced colitis model in GH-overexpressing mice. In this model, in addition to the GH-mediated effects on other immune cells, we observed that macrophages from inflamed gut acquire an anti-inflammatory/reparative profile. Overall, these data indicate that GH reprograms inflammatory macrophages to an anti-inflammatory phenotype and improves resolution during pathologic inflammatory responses.
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