The angiogenic factor PIGF mediates a neuroimmune interaction in the spleen to allow the onset of hypertension

Daniela Carnevale, Fabio Pallante, Valentina Fardella, Stefania Fardella, Roberta Iacobucci, Massimo Federici, Giuseppe Cifelli, Massimiliano DeLucia, Giuseppe Lembo

Research output: Contribution to journalArticlepeer-review

Abstract

Hypertension is a health problem affecting over 1 billion people worldwide. How the immune systemgets activated under hypertensive stimuli to contribute to blood pressure elevation is a fascinating enigma. Here we showed a splenic role for placental growth factor (PlGF), which accounts for the onset of hypertension, through immune system modulation. PlGF repressed the expression of the protein Timp3 (tissue inhibitor of metalloproteinases 3), through the transcriptional Sirt1-p53 axis. Timp3 repression allowed costimulation of Tcells and their deployment toward classical organs involved in hypertension. We showed that the spleen is an essential organ for the development of hypertension through anoradrenergic drive mediated by the celiac ganglionefferent. Overall, we demonstrate that PlGF mediates the neuroimmune interaction in the spleen, organizing a unique and nonredundant response that allows the onset of hypertension.

Original languageEnglish
Pages (from-to)737-752
Number of pages16
JournalImmunity
Volume41
Issue number5
DOIs
Publication statusPublished - Nov 20 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology
  • Medicine(all)

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