The intraepithelial T cell response to NKG2D-ligands links lymphoid stress surveillance to atopy

Science. 2011 Dec 2;334(6060):1293-7. doi: 10.1126/science.1211250.

Abstract

Epithelial cells respond to physicochemical damage with up-regulation of major histocompatibility complex-like ligands that can activate the cytolytic potential of neighboring intraepithelial T cells by binding the activating receptor, NKG2D. The systemic implications of this lymphoid stress-surveillance response, however, are unknown. We found that antigens encountered at the same time as cutaneous epithelial stress induced strong primary and secondary systemic, T helper 2 (T(H)2)-associated atopic responses in mice. These responses required NKG2D-dependent communication between dysregulated epithelial cells and tissue-associated lymphoid cells. These data are germane to uncertainty over the afferent induction of T(H)2 responses and provide a molecular framework for considering atopy as an important component of the response to tissue damage and carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epidermis / immunology*
  • Hypersensitivity, Immediate / immunology*
  • Ligands
  • Lymphoid Tissue / immunology*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • NK Cell Lectin-Like Receptor Subfamily K / immunology
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Stress, Physiological
  • T-Lymphocyte Subsets / immunology*
  • Th2 Cells / immunology*
  • Up-Regulation

Substances

  • Klrk1 protein, mouse
  • Ligands
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Raet1b protein, mouse
  • Receptors, Antigen, T-Cell, gamma-delta