IL4 Gene

IL4 (interleukin 4) is a protein-coding gene that is loaclized on chromosome 5q31.1. The protein encoded by the IL4 gene, the pleiotropic cytokine IL-4, is a type 2 cytokine produced by activated T cells. IL-4 is considered an important cytokine for "tissue repair" that counterbalances the effects of proinflammatory type 1 cytokines. In addition, IL-4 mediates and regulates a variety of human host responses, including allergic, antiparasitic, wound healing, and acute inflammation.

The IL4 gene, along with the IL3, IL5, IL13, and CSF2 genes, form a cytokine gene cluster on chromosome 5q, with the IL4 gene being particularly close to IL13. Thus, the IL4 gene, together with the IL13 and IL5 genes, have been shown to be coordinately regulated by multiple overlapping regulatory elements in a region of over 120 kilobases on the chromosome. IL-4, along with IL-13, is one of the two ligands for the interleukin-4 receptor. This peculiarity leads to many overlapping functions.

In an allergic reaction, IL-4 plays an essential role in the production of allergen-specific immunoglobin (Ig) E. IL-4 is elevated in COVID-19 patients but is not necessarily associated with severe COVID-19 pathology.

Diseases associated with polymorphisms in the IL4 gene include:

• Chronic peridontitis (Ksiazek K et al 2019).
• Autoimmune hepatitis (Yousefi A et al 2016).
• Rheumatoid arthritis (Park HK et al 2017).
• Allergic diseases such as atopic dermatitis.
• Lumbar disc disease: evidence of polymorphisms of the IL4 and IL6 genes (Zhu Yet al. 2017)

STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immunoregulatory signal of this cytokine.

Ksiazek K et al (2019) IL4 gene VNTR polymorphism in chronic periodontitis in end-stage renal disease patients. Oral Dis 25:258-264.

1. Liu X, Beaty TH, Deindl P, Huang SK, Lau S, Sommerfeld C, Fallin MD, Kao WH, Wahn U, Nickel R. Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study. J Allergy Clin Immunol. 2004 Mar;113(3):489-95.
2. Park HKet al. (2017) Promoter polymorphism (-590, T/C) of interleukin 4 (IL4) gene is associated with rheumatoid arthritis: An updated meta-analysis. Saudi J Biol Sci 24: 444-449.
3. Taylor JJ et al (2009) Th2 cell hyporesponsiveness during chronic murine schistosomiasis is cell intrinsic and linked to GRAIL expression. J Clin Invest 119:1019-1028.
4. Yousefi A et al (2016) IL4 gene polymorphisms in Iranian patients with autoimmune hepatitis. Expert Rev Gastroenterol Hepatol 10:659-663.
5. Zhu Yet al. (2017) Association between IL4, IL6 gene polymorphism and lumbar disc degeneration in Chinese population. Oncotarget 8:89064-89071.