Interleukin 4

1BBN, 1BCN, 1CYL, 1HIJ, 1HIK, 1HZI, 1IAR, 1ITI, 1ITL, 1ITM, 1RCB, 2B8U, 2B8X, 2B8Y, 2B8Z, 2B90, 2B91, 2CYK, 2D48, 2INT, 3BPL, 3BPN, 3QB7, 4YDY, 5FHX356516189ENSG00000113520ENSMUSG00000000869P05112P07750NM_172348NM_000589NM_001354990NM_021283NP_000580NP_758858NP_001341919NP_067258The 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. The cell that initially produces IL-4, thus inducing Th2 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell. It is closely related and has functions similar to interleukin 13.1bbn: THREE-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-4 BY MULTI-DIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY1bcn: THREE-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-4 BY MULTI-DIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY1cyl: ASPECTS OF RECEPTOR BINDING AND SIGNALLING OF INTERLEUKIN-4 INVESTIGATED BY SITE-DIRECTED MUTAGENESIS AND NMR SPECTROSCOPY1hij: INTERLEUKIN-4 MUTANT WITH ARG 88 REPLACED WITH GLN (R88Q)1hik: INTERLEUKIN-4 (WILD-TYPE)1hzi: INTERLEUKIN-4 MUTANT E9A1iar: INTERLEUKIN-4 / RECEPTOR ALPHA CHAIN COMPLEX1iti: THE HIGH RESOLUTION THREE-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-4 DETERMINED BY MULTI-DIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY1itl: HUMAN INTERLEUKIN 4: THE SOLUTION STRUCTURE OF A FOUR-HELIX-BUNDLE PROTEIN1itm: ANALYSIS OF THE SOLUTION STRUCTURE OF HUMAN INTERLEUKIN 4 DETERMINED BY HETERONUCLEAR THREE-DIMENSIONAL NUCLEAR MAGNETIC RESONANCE TECHNIQUES1rcb: CRYSTAL STRUCTURE OF HUMAN RECOMBINANT INTERLEUKIN-4 AT 2.25 ANGSTROMS RESOLUTION2b8u: Crystal structure of wildtype human Interleukin-42b8x: Crystal structure of the interleukin-4 variant F82D2b8y: Crystal structure of the interleukin-4 variant T13DF82D2b8z: Crystal structure of the interleukin-4 variant R85A2b90: Crystal structure of the interleukin-4 variant T13DR85A2b91: Crystal structure of the interleukin-4 variant F82DR85A2cyk: ASPECTS OF RECEPTOR BINDING AND SIGNALLING OF INTERLEUKIN-4 INVESTIGATED BY SITE-DIRECTED MUTAGENESIS AND NMR SPECTROSCOPY2d48: Crystal structure of the Interleukin-4 variant T13D2int: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN 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. The cell that initially produces IL-4, thus inducing Th2 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell. It is closely related and has functions similar to interleukin 13. Interleukin 4 has many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and the differentiation of B cells into plasma cells. It is a key regulator in humoral and adaptive immunity. IL-4 induces B-cell class switching to IgE, and up-regulates MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, and dendritic cell IL-12. Overproduction of IL-4 is associated with allergies. Tissue macrophages play an important role in chronic inflammation and wound repair. The presence of IL-4 in extravascular tissues promotes alternative activation of macrophages into M2 cells and inhibits classical activation of macrophages into M1 cells. An increase in repair macrophages (M2) is coupled with secretion of IL-10 and TGF-β that result in a diminution of pathological inflammation. Release of arginase, proline, polyaminases and TGF-β by the activated M2 cell is tied with wound repair and fibrosis. The receptor for interleukin-4 is known as the IL-4Rα. This receptor exists in 3 different complexes throughout the body. Type 1 receptors are composed of the IL-4Rα subunit with a common γ chain and specifically bind IL-4. Type 2 receptors consist of an IL-4Rα subunit bound to a different subunit known as IL-13Rα1. These type 2 receptors have the ability to bind both IL-4 and IL-13, two cytokines with closely related biological functions. IL-4 has a compact, globular fold (similar to other cytokines), stabilised by 3 disulphide bonds. One half of the structure is dominated by a 4 alpha-helix bundle with a left-handed twist. The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet. This cytokine was co-discovered by Maureen Howard and William E. Paul as well as by Ellen Vitetta and her research group in 1982. The nucleotide sequence for human IL-4 was isolated four years later confirming its similarity to a mouse protein called B-cell stimulatory factor-1 (BCSF-1). IL-4 has been found to mediate a crosstalk between the neural stem cells and neurons that undergo neurodegeneration, and initiate a regeneration cascade through phosphorylation of its intracellular effector STAT6 in an experimental Alzheimer's disease model in adult zebrafish brain.