Resistance to experimental autoimmune encephalomyelitis and impaired IL-17 production in protein kinase C theta-deficient mice

J Immunol. 2006 Mar 1;176(5):2872-9. doi: 10.4049/jimmunol.176.5.2872.


The protein kinase C theta (PKC theta) serine/threonine kinase has been implicated in signaling of T cell activation, proliferation, and cytokine production. However, the in vivo consequences of ablation of PKC theta on T cell function in inflammatory autoimmune disease have not been thoroughly examined. In this study we used PKC theta-deficient mice to investigate the potential involvement of PKC theta in the development of experimental autoimmune encephalomyelitis, a prototypic T cell-mediated autoimmune disease model of the CNS. We found that PKC theta-/- mice immunized with the myelin oligodendrocyte glycoprotein (MOG) peptide MOG(35-55) were completely resistant to the development of clinical experimental autoimmune encephalomyelitis compared with wild-type control mice. Flow cytometric and histopathological analysis of the CNS revealed profound reduction of both T cell and macrophage infiltration and demyelination. Ex vivo MOG(35-55) stimulation of splenic T lymphocytes from immunized PKC theta-/- mice revealed significantly reduced production of the Th1 cytokine IFN-gamma as well as the T cell effector cytokine IL-17 despite comparable levels of IL-2 and IL-4 and similar cell proliferative responses. Furthermore, IL-17 expression was dramatically reduced in the CNS of PKC theta-/- mice compared with wild-type mice during the disease course. In addition, PKC theta-/- T cells failed to up-regulate LFA-1 expression in response to TCR activation, and LFA-1 expression was also significantly reduced in the spleens of MOG(35-55)-immunized PKC theta-/- mice as well as in in vitro-stimulated CD4+ T cells compared with wild-type mice. These results underscore the importance of PKC theta in the regulation of multiple T cell functions necessary for the development of autoimmune disease.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Disease Susceptibility
  • Encephalomyelitis, Autoimmune, Experimental / enzymology*
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Glycoproteins / immunology
  • Immunity, Innate / genetics
  • Interferon-gamma / biosynthesis
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / biosynthesis*
  • Isoenzymes / deficiency*
  • Isoenzymes / genetics*
  • Isoenzymes / physiology
  • Lymphocyte Function-Associated Antigen-1 / biosynthesis
  • Lymphocyte Function-Associated Antigen-1 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments / immunology
  • Protein Kinase C / deficiency*
  • Protein Kinase C / genetics*
  • Protein Kinase C / physiology
  • Protein Kinase C-theta
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism


  • Glycoproteins
  • Interleukin-17
  • Isoenzymes
  • Lymphocyte Function-Associated Antigen-1
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • Interferon-gamma
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta