The interleukin 4 receptor is a
type I cytokine receptor. IL4R is its human
gene.
Function
This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind
interleukin 4 and
interleukin 13 to regulate
IgE antibody production in
B cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
s. Among
T cells, the encoded protein also can bind interleukin 4 to promote differentiation of
Th2 cells. A soluble form of the encoded protein can be produced by an alternate splice variant or by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitis, asthma, or eczema. Two transcript variants encoding different isoforms, a membrane-bound and a soluble form, have been found for this gene. Interactions of IL-4 with
TNFα
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
promote structural changes to vascular endothelial cells, thus playing an important role in tissue inflammation.
The binding of IL-4 or IL-13 to the IL-4 receptor on the surface of
macrophages results in the alternative activation of those macrophages. Alternatively activated macrophages (AAMΦ) downregulate inflammatory mediators such as
IFNγ during immune responses, particularly with regards to
helminth
Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as schi ...
infections.
IL4 signalling also determines the levels of CD20 on normal and malignant B cells by activation the transcription factor STAT6.
Interactions
Interleukin-4 receptor has been shown to
interact with
SHC1.
Structure
The
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
(
extracellular) portion of interleukin-4 receptor is related in overall topology to
fibronectin type III modules and
fold
Fold, folding or foldable may refer to:
Arts, entertainment, and media
* ''Fold'' (album), the debut release by Australian rock band Epicure
*Fold (poker), in the game of poker, to discard one's hand and forfeit interest in the current pot
*Above ...
s into a sandwich comprising seven
antiparallel beta sheets arranged in a three-strand and a four-strand
beta-pleated sheet. They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of a
Th2
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
-dominated early
immune response.
See also
*
Macrophage-activating factor
*
Macrophage polarization
*
Cluster of differentiation
*
Fibronectin type III domain
References
Further reading
*
*
External links
*
PDBe-KBprovides an overview of all the structure information available in the PDB for Human Interleukin-4 receptor subunit alpha
{{InterPro content, IPR015319
Type I cytokine receptors
Clusters of differentiation
Protein domains