Article Text

PDF
SP0150 Th17 cells drive and regulate tissue inflammation
  1. V Kuchroo,
  2. on behalf of Basic and Translation Science
  1. Evergrande Center for Immunologic Diseases, Harvard Medical School, Boston, United States

Abstract

Recently a subset of interleukin (IL)-17-producing T cells (TH17) distinct from TH1 or TH2 cells was described and shown to have a crucial role in the induction of autoimmune tissue injury. Accumulating data suggests that there are three distinct steps in Th17 differentiation: Induction, Amplification and Stabilization mediated by distinct cytokines. Whereas TGF-b + IL-6 or IL-1 + IL-6 induces them, IL-21 amplifies Th17 cells, IL-23 stabilizes the phenotype of Th17 cells. Loss of any of the cytokines (TGF-β, IL-1, IL-6, IL-21 or IL-23) in the pathway results in a defect in generation of Th17. However not all Th17 cells are pathogenic and induce autoimmunity, IL-23 is a key cytokine that induces pathogenicity in Th17 cells (Lee et al., 2012). Using expression profiling at very high temporal resolution, novel computational algorithms and innovative nano-wire based “knock-down” approaches, we have developed a regulatory network that governs the development of Th17 cells. In addition to high-density temporal microarray analysis, we have performed single-cell RNA-seq of Th17 cells in order to characterize cellular heterogeneity, identify subpopulations, functional states and learn how gene expression variation affects Th17 effector functions. We have identified novel regulators of Th17 cells both in vivo and in vitro that do not affect Th17 differentiation but affect pathogenic vs. non-pathogenic functional states of Th17 cells. Some of the regulators that make Th17 cells non-pathogenic are also utilized by CD8+ T cells to induce T cell “exhaustion” or “dysfunction”. These novel inhibitory molecules cooperate with other known “check-point” co-inhibitory receptors to suppress anti-tumor immunity.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.