IL-22, not simply a Th17 cytokine

Immunol Rev. 2013 Mar;252(1):116-32. doi: 10.1111/imr.12027.


Interleukin-22 (IL-22) has important functions in host defense at mucosal surfaces as well as in tissue repair. It is unique as a cytokine that is produced by immune cells, including T-helper (Th) cell subsets and innate lymphocytes, but acts only on non-hematopoietic stromal cells, in particular epithelial cells, keratinocytes, and hepatocytes. Although IL-22 is beneficial to the host in many infectious and inflammatory disorders, depending on the target tissue it can be pathogenic due to its inherent pro-inflammatory properties, which are further enhanced when IL-22 is released together with other pro-inflammatory cytokines, in particular IL-17. To avoid pathology, IL-22 and IL-17 production have to be controlled tightly and independently. While common factors such as signal transducer and activator of transcription 3 (STAT3) and retinoid orphan receptor γt (RORγt) drive the expression of both cytokines, other factors, such as c-Maf act specifically on IL-22 and enable the separate expression of either cytokine. Here, we discuss the production of IL-22 from various T-cell populations as well as protective versus pathogenic roles of IL-22. Finally, we focus on recent advances in our understanding of the molecular regulation of IL-22 in T cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate
  • Immunity, Mucosal
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukins / genetics
  • Interleukins / immunology*
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology*
  • Proto-Oncogene Proteins c-maf / genetics
  • Proto-Oncogene Proteins c-maf / immunology*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology*
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Interleukin-17
  • Interleukins
  • MAF protein, human
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Proto-Oncogene Proteins c-maf
  • RORC protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • interleukin-22