Opposing roles for IL-13 and IL-13 receptor alpha 2 in health and disease

Immunol Rev. 2004 Dec;202:191-202. doi: 10.1111/j.0105-2896.2004.00210.x.

Abstract

Interleukin (IL)-13 is a key inducer of several type-2 cytokine-dependent pathologies. It regulates inflammation, mucus production, tissue remodeling, and fibrosis. Consequently, it has become an important therapeutic target for a number of debilitating illnesses, including asthma, idiopathic pulmonary fibrosis, ulcerative colitis, as well as several other diseases in which IL-13 is believed to be overproduced. In the murine model of schistosomiasis, IL-13 has emerged as a central mediator of chronic infection-induced liver pathology. Although IL-4, IL-5, IL-10, and IL-13 each regulate distinct aspects of the granulomatous inflammatory response, IL-13 was identified as the primary mediator of liver fibrosis. Thus, elucidating the mechanisms that regulate the production and function of IL-13 has become an intensive area of research. IL-13 signaling is mediated by the type-2 IL-4 receptor, which consists of the IL-4R alpha and IL-13R alpha 1 chains. However, another IL-13-binding chain, IL-13R alpha 2, appears to strongly inhibit the activity of IL-13. Animals deficient in IL-13R alpha 2 fail to downmodulate granuloma formation in the chronic phase of infection. They also develop severe IL-13-dependent fibrosis and portal hypertension and quickly succumb to the infection. Here, we summarize findings from the schistosomiasis model, which illustrate opposing activities for IL-13 and IL-13R alpha 2 in health and disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Fibrosis
  • Granulomatous Disease, Chronic / etiology
  • Granulomatous Disease, Chronic / metabolism
  • Inflammation / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-13 / metabolism*
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / metabolism
  • Liver / metabolism
  • Liver / parasitology
  • Liver / pathology
  • Mice
  • Plasma Cell Granuloma, Pulmonary / etiology
  • Plasma Cell Granuloma, Pulmonary / metabolism
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-13
  • Schistosomiasis / metabolism

Substances

  • Il13ra1 protein, mouse
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Interleukin-4
  • Interferon-gamma