IL-17A-producing CD8(+)T cells as therapeutic targets in autoimmunity

Expert Opin Ther Targets. 2015 May;19(5):651-61. doi: 10.1517/14728222.2014.997710. Epub 2015 Jan 22.

Abstract

Introduction: The involvement of IL-17-producing CD8(+)T cells (TC17) in various conditions, such as infection, cancer and autoimmune inflammation, has been documented in both humans and mice; however, TC17 cells have received only marginal attention.

Areas covered: Here, we provide an overview of the cytokines, chemokines, and cytokine and chemokine receptors that characterize the murine and human TC17 cell phenotype. We also discuss signaling pathways, molecular interactions, and transcriptional and epigenetic events that contribute to TC17 differentiation and acquisition of effector functions. Heterogeneity and inherent phenotypic instability of TC17 cells were shown both in humans and murine models. Aberrant expression of TC17 cells was observed in many autoimmune conditions. Moreover, functional analysis demonstrated in vivo plasticity of TC17 cells may be a key feature of TC17 cell biology in autoimmune diseases.

Expert opinion: Due to its important roles in inflammation and autoimmunity, TC17 cell pathway may have promise as a potential therapeutic target for autoimmune diseases. The strategies include the suppression of TC17 cell generation and migration and the blockade of TC17 cell instability and heterogeneity. TMP778 may open an avenue to novel therapeutic strategies.

Keywords: CD8+T cells; IL-17; autoimmune diseases; immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy*
  • Autoimmunity / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cytokines / immunology
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Interleukin-17 / immunology*
  • Mice
  • Molecular Targeted Therapy
  • Th17 Cells / immunology

Substances

  • Cytokines
  • Heterocyclic Compounds, 4 or More Rings
  • Interleukin-17
  • TMP778