The interleukin 4 receptor is a
type I cytokine receptor. It is a
heterodimer, that is, composed of two subunits. IL4R is the human
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
coding for IL-4Rα, the subunit which combines with either
common gamma chain (γc, forming the type I
IL4 receptor) or with
IL-13Rα1 (forming the type II IL4 receptor).
Function
This gene encodes the alpha chain of the interleukin-4 receptor, a
type I transmembrane protein that can bind
interleukin 4
The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells ( Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 ...
and
interleukin 13 to regulate
IgE antibody
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
production in
B cell
B cells, also known as B lymphocytes, are a type 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 inserted into the plasm ...
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 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
Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
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 infections.
Interactions
Interleukin-4 receptor has been shown to
interact with
SHC1.
Structure
The
N-terminal (
extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
) portion of interleukin-4 receptor is related in overall topology to
fibronectin type III modules and
folds 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-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