Pathogenic IL-23 signaling is required to initiate GM-CSF-driven autoimmune myocarditis in mice

Lei Wu, Nicola L. Diny, Sufey Ong, Jobert G. Barin, Xuezhou Hou, Noel R. Rose, Monica V. Talor, Daniela Čiháková

Research output: Contribution to journalArticlepeer-review

Abstract

Using a mouse model of experimental autoimmune myocarditis (EAM), we showed for the first time that IL-23 stimulation of CD4+ T cells is required only briefly at the initiation of GM-CFS-dependent cardiac autoimmunity. IL-23 signal, acting as a switch, turns on pathogenicity of CD4+ T cells, and becomes dispensable once autoreactivity is established. Il23a-/- mice failed to mount an efficient Th17 response to immunization, and were protected from myocarditis. However, remarkably, transient IL-23 stimulation ex vivo fully restored pathogenicity in otherwise nonpathogenic CD4+ T cells raised from Il23a-/- donors. Thus, IL-23 may no longer be necessary to uphold inflammation in established autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)582-592
Number of pages11
JournalEuropean Journal of Immunology
Volume46
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • Autoimmunity
  • GM-CSF
  • IL-17A
  • IL-23
  • Myocarditis
  • Th17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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