IL13RA1 Gene

The IL13RA1 gene (IL13RA1 stands for: Interleukin 13 Receptor Subunit Alpha 1) is a protein-coding gene located on chromosome Xq24.

The protein encoded by the IL13RA1 gene is a subunit of the interleukin-13 receptor. This subunit forms a receptor complex with the IL4 receptor alpha, a common subunit of IL13 and IL4 receptors. This complex serves as the primary IL13-binding component of the IL13 receptor and may also be a component of the IL4 receptor. This protein has been shown to bind the tyrosine kinase TYK2 and thus may mediate the signaling processes leading to the activation of JAK1, STAT3 and STAT6 induced by IL13 and IL4.

The receptor binds to interleukin-13 (IL13) with only low affinity. Together with IL4RA, it can form a functional receptor for IL13 and also serves as an alternative accessory protein for the common cytokine receptor-gamma chain of interleukin-4 (IL4) signaling. The genomic locus where IL-4 and IL-13 (together with IL-5) are produced is called the Th2 cytokine locus, which in humans is located on chromosome 5.

However, the production of the two cytokines is not identical: IL-4 production is dependent on calcineurin, whereas IL-13 production is only partially dependent on calcineurin. Upon appropriate stimulation of the cells, the LCR of the Th2 cytokine locus is epigenetically modified to allow transcription factors to access the DNA and subsequently transcribe these cytokines. Here, a polymorphism in the murine equivalent of the DNase I hypersensitive site (RHS)7 in humans influences DNA methylation and gene expression on 5q31 and subsequently IgE levels at the population level.

Diseases associated with IL13RA1 include monofixation syndrome and asthma. Monofixation syndrome (MFS) (also known as microtropia or microstrabismus) is an eye disorder defined by imperfect binocular vision. It is defined by a small angular deviation with suppression of the deflected eye and the presence of binocular peripheral fusion. That is, MFS implies peripheral fusion without central fusion. MFS is a rare disorder and is estimated to affect only 1% of the total population. Primary MFS is thought to be the result of a primary sensory defect that predisposes to abnormal retinal correspondence.

The receptor binds to interleukin-13 (IL13) with only low affinity. Together with IL4RA, it can form a functional receptor for IL13 and also serves as an alternative accessory protein for the common cytokine receptor-gamma chain of interleukin-4 (IL4) signaling.

Interleukin (IL)-4 and IL-13 are related cytokines that regulate many aspects of allergic inflammation. They play an important role in regulating the responses of lymphocytes, myeloid cells and non-hematopoietic cells. In T cells, IL-4 induces the differentiation of naïve CD4 T cells into Th2 cells, in B cells IL-4 controls immunoglobulin (Ig) class switching to IgG1 and IgE, and in macrophages IL-4 and IL-13 induce alternative macrophage activation. This knowledge of IL-4 is of increasing clinical importance as therapeutic approaches targeting the cytokine and its signal transduction become part of clinical practice in the treatment of allergic diseases.

Interleukin-4 and interleukin-13 are the hallmark cytokines of the type II inflammatory response and play a key role in the inflammatory response triggered by either an invading parasite or an allergen. The cellular sources of IL-4 and IL-13 have been extensively studied, and in addition to CD4 T cells, basophils, eosinophils, mast cells and NK T cells, appropriately stimulated ILC2 cells have the ability to produce IL-4 and IL-13

1. Junttila IS (2018) Tuning the Cytokine Responses: An Update on Interleukin (IL)-4 and IL-13 Receptor Complexes. Front Immunol 9:888.
2. Tabata Y et al. (2007) IL-13 receptor isoforms: breaking through the complexity. Curr Allergy Asthma Rep 7:338-345.