Cytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transduction.
IL (interleukin)-4 and IL-13 are key cytokines in the pathogenesis of allergic inflammatory disease. IL-4 and IL-13 share many functional properties as a result of their utilization of a common receptor complex comprising IL-13Ralpha1 (IL-13 receptor alpha-chain 1) and IL-4Ralpha. The second IL-13R (IL-13 receptor) has been identified, namely IL-13Ralpha2. This has been thought to be a decoy receptor due to its short cytoplasmic tail and its high binding affinity for IL-13 but not IL-4. IL-13Ralpha2 exists on the cell membrane, intracellularly and in a soluble form. Recent reports revealed that membrane IL-13Ralpha2 may have some signalling capabilities, and a soluble form of IL-13Ralpha2 can be generated in the presence of environmental allergens such as DerP. Interestingly, IL-13Ralpha2 has also been shown to regulate both IL-13 and IL-4 response in primary airway cells, despite the fact that IL-13Ralpha2 does not bind IL-4. The regulator mechanism is still unclear but the physical association of IL-13Ralpha2 with IL-4Ralpha appears to be a key regulatory step. These results suggest that the cytoplasmic tail of IL-13Ralpha2 may interfere with the association or activation of signalling molecules, such as JAK1 (Janus kinase 1), on IL-4Ralpha and thus prevents downstream signal cascade. The receptor has more complicated functions than a simple decoy receptor. In this review, we discuss newly revealed functions of IL-13Ralpha2.
Andrews
Allison-Lynn
AL
School of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. ala@soton.ac.uk
Nordgren
Ida Karin
IK
Kirby
Isabelle
I
Holloway
John W
JW
Holgate
Stephen T
ST
Davies
Donna E
DE
Tavassoli
Ali
A
D000818:Animals; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000378:metabolism / Q000502:physiology*; D015847:Interleukin-4 / Q000378:metabolism*; D053660:Receptors, Interleukin-13 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D053660:Receptors, Interleukin-13; D015847:Interleukin-4