Interleukin 13

Interleukin 13 (IL-13) is a cytokine secreted by many cell types, but especially T helper type 2 (Th2) cellsWynn TA. IL-13 effector functions. Annu Rev Immunol. 2003;21:425-56.] , that is an important mediator of allergic inflammation and disease.

Functions

In addition to effects on immune cells that are similar to those of the closely related cytokine IL-4, IL-13 is more importantly implicated as a central mediator of the physiologic changes induced by allergic inflammation in many tissues. IL-13 induces its effects through a multi-subunit receptor that includes the alpha chain of the IL-4 receptor (IL-4Rα), which is also a component of the IL-4 receptor, and at least one of two known IL-13-specific binding chainsWynn TA. IL-13 effector functions. Annu Rev Immunol. 2003;21:425-56.] . Most of the biological effects of IL-13, like those of IL-4, are linked to a single transcription factor, signal transducer and activator of transcription 6 (STAT6).

The functions of IL-13 overlap considerably with those of IL-4, especially with regard to changes induced on hematopoietic cells, but these effects are probably less important given the more potent role of IL-4. Thus, although IL-13 can induce immunoglobulin E (IgE) secretion from activated human B cells, deletion of IL-13 from mice does not markedly affect either Th2 cell development or antigen-specific IgE responses induced by potent allergens. In comparison, deletion of IL-4 abrogates these responses. Thus, rather than a lymphoid cytokine, IL-13 acts more prominently as a molecular bridge linking allergic inflammatory cells to the non-immune cells in contact with them, thereby altering physiological function.

Although IL-13 is associated primarily with the induction of airway disease, it also has anti-inflammatory properties. Airway matrix metalloproteinases (MMPs), which are protein-degrading enzymes, are required to induce egression of effete parenchymal inflammatory cells into the airway lumen where they are then cleared. Among other factors, IL-13 induces these MMPs as part of a mechanism that protects against excessive allergic inflammation that predisposes to asphyxiation.

Clinical significance

IL-13 specifically induces physiological changes in parasitized organs that are required to expel the offending organisms or their products. For example, expulsion from the gut of a variety of mouse helminths requires IL-13 secreted by Th2 cells. IL-13 induces several changes in the gut that create an environment hostile to the parasite, including enhanced contractions and glycoprotein hyper-secretion from gut epithelial cells, that ultimately lead to detachment of the organism from the gut wall and their removal.

The eggs of the parasite "Schistosoma mansoni" may lodge in a variety of organs including the gut wall, liver, lung and even central nervous system, inducing the formation of granulomas under the control of IL-13. Here, however, the eventual result is organ damage and often profound or even fatal disease, not resolution of the infection. An emerging concept is that IL-13 may antagonize Th1 responses that are required to resolve intracellular infections. In this immune dysregulated context, marked by the recruitment of aberrantly large numbers of Th2 cells, IL-13 inhibits the ability of host immune cells to destroy intracellular pathogens.

IL-13 induces many features of allergic lung disease, including airway hyperresponsiveness, goblet cell metaplasia and mucus hypersecretion, which all contribute to airway obstruction Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL & Donaldson DD. Interleukin-13: central mediator of allergic asthma. Science 282, 2258-2261.] . IL-4 contributes to these physiologic changes, but is less important than IL-13. IL-13 also induces secretion of chemokines that are required for recruitment of allergic effector cells to the lung. Studies of STAT6 transgenic mice suggest the interesting possibility that IL-13 signaling occurring only through the airway epithelium is required for most of these effects. While no studies have yet directly implicated IL-13 in the control of human diseases, many polymorphisms in the IL-13 gene have been shown to confer an enhanced risk of atopic respiratory diseases such as asthma.

ee also

IL-13R, the IL-13 receptor

References

Further reading

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citations =
*cite journal | author=Marone G, Florio G, Petraroli A, de Paulis A |title=Dysregulation of the IgE/Fc epsilon RI network in HIV-1 infection. |journal=J. Allergy Clin. Immunol. |volume=107 |issue= 1 |pages= 22–30 |year= 2001 |pmid= 11149986 |doi=
*cite journal | author=Marone G, Florio G, Triggiani M, "et al." |title=Mechanisms of IgE elevation in HIV-1 infection. |journal=Crit. Rev. Immunol. |volume=20 |issue= 6 |pages= 477–96 |year= 2001 |pmid= 11396683 |doi=
*cite journal | author=Skinnider BF, Kapp U, Mak TW |title=The role of interleukin 13 in classical Hodgkin lymphoma. |journal=Leuk. Lymphoma |volume=43 |issue= 6 |pages= 1203–10 |year= 2003 |pmid= 12152987 |doi=
*cite journal | author=Izuhara K, Arima K, Yasunaga S |title=IL-4 and IL-13: their pathological roles in allergic diseases and their potential in developing new therapies. |journal=Current drug targets. Inflammation and allergy |volume=1 |issue= 3 |pages= 263–9 |year= 2003 |pmid= 14561191 |doi=
*cite journal | author=Dessein A, Kouriba B, Eboumbou C, "et al." |title=Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis. |journal=Immunol. Rev. |volume=201 |issue= |pages= 180–90 |year= 2005 |pmid= 15361241 |doi= 10.1111/j.0105-2896.2004.00195.x
*cite journal | author=Copeland KF |title=Modulation of HIV-1 transcription by cytokines and chemokines. |journal=Mini reviews in medicinal chemistry |volume=5 |issue= 12 |pages= 1093–101 |year= 2006 |pmid= 16375755 |doi=

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