IL-13 receptors and signaling pathways: an evolving web

J Allergy Clin Immunol. 2003 Apr;111(4):677-90; quiz 691. doi: 10.1067/mai.2003.1333.


IL-13 is an immunoregulatory cytokine secreted predominantly by activated T(H)2 cells. Over the past several years, it has become evident that IL-13 is a key mediator in the pathogenesis of allergic inflammation. IL-13 shares many functional properties with IL-4, stemming from the fact that they share a common receptor subunit, the alpha subunit of the IL-4 receptor (IL-4Ralpha). Characterization of IL-13-deficient mice, IL-4-deficient mice, and IL-4 receptor alpha-deficient (IL-4Ralpha(-/-)) mice have demonstrated nonredundant roles for IL-13. IL-13 mediates its effects by interacting with a complex receptor system comprised of IL-4Ralpha and two IL-13 binding proteins, IL-13Ralpha1 and IL-13Ralpha2. IL-13 receptors are expressed on human B cells, basophils, eosinophils, mast cells, endothelial cells, fibroblasts, monocytes, macrophages, respiratory epithelial cells, and smooth muscle cells. However, functional IL-13 receptors have not been demonstrated on human or mouse T cells. Thus unlike IL-4, IL-13 does not appear to be important in the initial differentiation of CD4 T cells into T(H)2-type cells but rather appears to be important in the effector phase of allergic inflammation. This is further supported by many in vivo observations, including that administration of IL-13 resulted in allergic inflammation, tissue-specific overexpression of IL-13 in the lungs of transgenic mice resulted in airway inflammation and mucus hypersecretion, IL-13 blockade abolished allergic inflammation independently of IL-4, and IL-13 appears to be more important than IL-4 in mucus hypersecretion. Given the importance of IL-13 as an effector molecule, regulation at the level of its receptors might be an important mechanism of modulating IL-13 responses and thus propagation of the allergic response. Accordingly, IL-13 is an attractive, novel therapeutic target for pharmacologic intervention in allergic disorders. This review will summarize the current understanding of the IL-13 receptors and signaling pathways, emphasizing recent observations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cytokines / physiology
  • Humans
  • Interleukin-13 / chemistry
  • Interleukin-13 / genetics
  • Interleukin-13 / physiology
  • Interleukin-13 Receptor alpha1 Subunit
  • Janus Kinase 1
  • Protein-Tyrosine Kinases / physiology
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4 / physiology
  • STAT6 Transcription Factor
  • Signal Transduction / physiology*
  • Trans-Activators / physiology
  • src Homology Domains


  • Cytokines
  • IL13RA1 protein, human
  • Il13ra1 protein, mouse
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Trans-Activators
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • Jak1 protein, mouse
  • Janus Kinase 1