Interleukin 10 modulation of pathogenic Th17 cells during fatal alphavirus encephalomyelitis

Kirsten A. Kulcsar, Victoria K. Baxter, Ivorlyne P. Greene, Diane E. Griffin

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Mosquito-borne alphaviruses are important causes of epidemic encephalomyelitis. Neuronal cell death during fatal alphavirus encephalomyelitis is immune-mediated; however, the types of cells involved and their regulation have not been determined. We show that the virus-induced inflammatory response was accompanied by production of the regulatory cytokine IL-10, and in the absence of IL-10, paralytic disease occurred earlier and mice died faster. To determine the reason for accelerated disease in the absence of IL-10, immune responses in the CNS of IL-10-/- and wild-type (WT) mice were compared. There were no differences in the amounts of brain inflammation or peak virus replication; however, IL-10-/- animals had accelerated and increased infiltration of CD4+IL-17A+ and CD4+IL-17A+IFNγ+ cells compared with WT animals. Th17 cells infiltrating the brain demonstrated a pathogenic phenotype with the expression of the transcription factor, Tbet, and the production of granzyme B, IL-22, and GM-CSF, with greater production of GM-CSF in IL-10-/- mice. Therefore, in fatal alphavirus encephalomyelitis, pathogenic Th17 cells enter the CNS at the onset of neurologic disease and, in the absence of IL-10, appear earlier, develop into Th1/Th17 cells more often, and have greater production of GM-CSF. This study demonstrates a role for pathogenic Th17 cells in fatal viral encephalitis.

Original languageEnglish (US)
Pages (from-to)16053-16058
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number45
StatePublished - Nov 11 2014


  • GM-CSF
  • Immunopathology
  • Interleukin-10
  • Sindbis virus
  • Viral encephalitis

ASJC Scopus subject areas

  • General


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