Interleukin-22 but Not interleukin-17 Provides Protection to Hepatocytes During Acute Liver Inflammation

Immunity. 2007 Oct;27(4):647-59. doi: 10.1016/j.immuni.2007.07.023. Epub 2007 Oct 4.

Abstract

The cytokine interleukin-22 (IL-22) is primarily expressed by T helper 17 (Th17) CD4(+) T cells and is highly upregulated during chronic inflammatory diseases. IL-22 receptor expression is absent on immune cells, but is instead restricted to the tissues, providing signaling directionality from the immune system to the tissues. However, the role of IL-22 in inflammatory responses has been confounded by data suggesting both pro- and anti-inflammatory functions. Herein, we provide evidence that during inflammation, IL-22 played a protective role in preventing tissue injury. Hepatocytes from mice deficient in IL-22 were highly sensitive to the detrimental immune response associated with hepatitis. Additionally, IL-22-expressing Th17 cells provided protection during hepatitis in IL-22-deficient mice. On the other hand, interleukin-17 (IL-17), which is coexpressed with IL-22 and can induce similar cellular responses, had no observable role in liver inflammation. Our data suggest that IL-22 serves as a protective molecule to counteract the destructive nature of the immune response to limit tissue damage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Hepatitis / immunology*
  • Hepatitis / metabolism
  • Hepatocytes / immunology*
  • Hepatocytes / metabolism
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Mice
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • Interleukin-17
  • Interleukin-6
  • Interleukins
  • RNA, Messenger
  • interleukin-22