IL-23-driven encephalo-tropism and Th17 polarization during CNS-inflammation in vivo

Authors

  • Gabor Gyülvészi,

    1. Department of Pathology, Institute of Experimental Immunology, University Hospital of Zürich, Zürich, Switzerland
    Search for more papers by this author
  • Stefan Haak,

    1. Department of Pathology, Institute of Experimental Immunology, University Hospital of Zürich, Zürich, Switzerland
    Search for more papers by this author
  • Burkhard Becher

    Corresponding author
    1. Department of Pathology, Institute of Experimental Immunology, University Hospital of Zürich, Zürich, Switzerland
    • Department of Pathology, Institute of Experimental Immunology, University Hospital of Zürich, Winterthurer Strasse 190, CH-8057 Zürich, Switzerland Fax: +41-44-635-6883

    Search for more papers by this author

Abstract

IL-23 but not IL-12 is essential for the development of autoimmune tissue inflammation in mice. Conversely, IL-12 and IL-23 impact on the polarization of Th1 and Th17 cells, respectively. While both polarized T helper populations can mediate autoimmune inflammation, their redundancy in the pathogenesis of EAE indicates that IL-23 exerts its crucial influence on the disease independent of its T helper polarizing capacity. To study the impact of IL-23 and IL-12 on the behavior of encephalitogenic T cells in vivo, we generated BM-chimeric mice in which we can trace individual populations of IL-23 or IL-12 responsive T helper cells during EAE. We observed that T cells, which lack IL-12Rβ1 (no IL-12 and IL-23 signaling), fail to invade the CNS and do not acquire a Th17 phenotype. In contrast, loss of IL-12 signaling prevents Th1 polarization but does not prevent T-cell entry into the CNS. The loss of IL-12R engagement does not appear to alter T-cell expansion but leads to their accumulation in secondary lymphoid organs. We found that IL-23 licenses T cells to invade the target tissue and to exert their effector function, whereas IL-12 is critical for Th1 differentiation, but does not influence the pathogenic capacity of auto-reactive T helper cells in vivo.

Ancillary