IL-15 functions as a danger signal to regulate tissue-resident T cells and tissue destruction

Nat Rev Immunol. 2015 Dec;15(12):771-83. doi: 10.1038/nri3919. Epub 2015 Nov 16.


In this Opinion article, we discuss the function of tissues as a crucial checkpoint for the regulation of effector T cell responses, and the notion that interleukin-15 (IL-15) functions as a danger molecule that communicates to the immune system that the tissue is under attack and poises it to mediate tissue destruction. More specifically, we propose that expression of IL-15 in tissues promotes T helper 1 cell-mediated immunity and provides co-stimulatory signals to effector cytotoxic T cells to exert their effector functions and drive tissue destruction. Therefore, we think that IL-15 contributes to tissue protection by promoting the elimination of infected cells but that when its expression is chronically dysregulated, it can promote the development of complex T cell-mediated disorders associated with tissue destruction, such as coeliac disease and type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Infections / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Celiac Disease / immunology
  • Celiac Disease / metabolism
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism
  • Humans
  • Immunity, Cellular / immunology*
  • Interleukin-15 / immunology*
  • Interleukin-15 / metabolism
  • Interleukin-15 Receptor alpha Subunit / immunology
  • Interleukin-15 Receptor alpha Subunit / metabolism
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Models, Immunological
  • Protein Binding / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism


  • Interleukin-15
  • Interleukin-15 Receptor alpha Subunit