Effect of IL-10 Deficiency on TGFβ Expression during Fatal Alphavirus Encephalomyelitis in C57Bl/6 Mice

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Sindbis virus (SINV) causes viral encephalitis in mice with strain-dependent virulence. Fatal encephalomyelitis in C57Bl/6 mice infected with a neuroadapted strain of SINV (NSV) is an immunopathogenic process that involves Th17 cells modulated by the regulatory cytokine IL-10. To further characterize the pathogenic immune response to NSV, we analyzed the regulation of transforming growth factor (TGF)-b in both wild-type (WT) and IL-10-deficient mice. NSV infection upregulated the expression of TGFb1 and TGFb3 in the central nervous system (CNS). In the absence of IL-10, levels of brain Tgfb1 mRNA and brain and spinal cord mature active TGFβ1 and TGFβ3 proteins were higher than in WT mice. Compared to WT mice, IL-10-deficient mice had more TGFβ1-expressing type 3 innate lymphoid cells (ILC3s) and CD4+ T cells infiltrating the CNS, but similar numbers in the cervical lymph nodes. Expression of glycoprotein A repetitions predominant protein (GARP) that binds pro-TGFb on the surface of regulatory T cells was decreased on CNS cells from IL-10-deficient mice. Higher CNS TGFb was accompanied by more expression of TGFbRII receptor, activation of SMAD transcription factors, increased PCKα mRNA, and more RORγt-positive and IL-17A-expressing cells. These results suggest a compensatory role for TGFβ in the absence of IL-10 that fosters Th17-related immunopathology and more rapid death after NSV infection.

Original languageEnglish (US)
Article number1791
Issue number8
StatePublished - Aug 2022


  • encephalomyelitis
  • inflammation
  • innate lymphoid cells
  • mice
  • neuroadapted Sindbis virus
  • transforming growth factor beta

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology


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