Interleukin 13

Interleukin 13
PDB rendering based on 1ga3.
Available structures PDB 1GA3, 1IJZ, 1IK0, 1J9U, 3BPO, 3G6D, 3ITR, 3ITS, 3L5W, 3L5X, 3L5Y, 3LB6
Identifiers
Symbols	IL13; ALRH; BHR1; IL-13; P600
External IDs	OMIM: 147683 MGI: 96541 HomoloGene: 1649 GeneCards: IL13 Gene
Gene Ontology Molecular function • cytokine activity • interleukin-13 receptor binding • protein binding Cellular component • extracellular region • extracellular space • soluble fraction • cytoplasm • external side of plasma membrane Biological process • positive regulation of immunoglobulin production • cellular component movement • inflammatory response • immune response • signal transduction • cell-cell signaling • regulation of proton transport • positive regulation of B cell proliferation • response to lipopolysaccharide • response to nicotine • positive regulation of macrophage activation • positive regulation of ion transport • response to ethanol • positive regulation of smooth muscle cell proliferation • positive regulation of protein secretion • positive regulation of release of sequestered calcium ion into cytosol • cellular response to mechanical stimulus • cellular response to cytokine stimulus • negative regulation of transforming growth factor beta production Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3596	16163
Ensembl	ENSG00000169194	ENSMUSG00000020383
UniProt	P35225	P20109
RefSeq (mRNA)	NM_002188.2	NM_008355.3
RefSeq (protein)	NP_002179.2	NP_032381.1
Location (UCSC)	Chr 5: 131.99 – 132 Mb	Chr 11: 53.44 – 53.45 Mb
PubMed search	[1]	[2]

Interleukin 13 (IL-13) is a protein that in humans is encoded by the IL13 gene. IL-13 is cytokine secreted by many cell types, but especially T helper type 2 (Th2) cells, that is a 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) and at least one of two known IL-13-specific binding chains. 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). This can be resulted from an allergic reaction brought about when facing an Ala gene.

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. 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.

See also

• Interleukin-13 receptor, the IL-13 receptor

Further reading

• Marone G, Florio G, Petraroli A, de Paulis A (2001). "Dysregulation of the IgE/Fc epsilon RI network in HIV-1 infection.". J. Allergy Clin. Immunol. 107 (1): 22–30. doi:10.1067/mai.2001.111589. PMID 11149986. 
• Marone G, Florio G, Triggiani M, et al. (2001). "Mechanisms of IgE elevation in HIV-1 infection.". Crit. Rev. Immunol. 20 (6): 477–96. PMID 11396683. 
• Skinnider BF, Kapp U, Mak TW (2003). "The role of interleukin 13 in classical Hodgkin lymphoma.". Leuk. Lymphoma 43 (6): 1203–10. doi:10.1080/10428190290026259. PMID 12152987. 
• Izuhara K, Arima K, Yasunaga S (2003). "IL-4 and IL-13: their pathological roles in allergic diseases and their potential in developing new therapies.". Current drug targets. Inflammation and allergy 1 (3): 263–9. doi:10.2174/1568010023344661. PMID 14561191. 
• Dessein A, Kouriba B, Eboumbou C, et al. (2005). "Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis.". Immunol. Rev. 201: 180–90. doi:10.1111/j.0105-2896.2004.00195.x. PMID 15361241. 
• Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines.". Mini reviews in medicinal chemistry 5 (12): 1093–101. doi:10.2174/138955705774933383. PMID 16375755.