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'''Interleukin 5''' ('''IL5''') is an [[interleukin]] produced by type-2 [[T helper cell]]s and [[mast cells]].
{{GNF_Protein_box
 
| image = IL5_Crystal_Structure.rsh.png
 
| image_source = Crystal structure of human IL-5
 
| PDB = {{PDB2|1hul}}
 
| Name = Interleukin 5 (colony-stimulating factor, eosinophil)
 
| HGNCid = 6016
 
| Symbol = IL5
 
| AltSymbols =; EDF; IL-5; TRF
 
| OMIM = 147850
 
| ECnumber = 
 
| Homologene = 679
 
| MGIid = 96557
 
| GeneAtlas_image1 = PBB_GE_IL5_207952_at_tn.png
 
| Function = {{GNF_GO|id=GO:0005125 |text = cytokine activity}} {{GNF_GO|id=GO:0005137 |text = interleukin-5 receptor binding}}
 
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}}
 
| Process = {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0050731 |text = positive regulation of peptidyl-tyrosine phosphorylation}}
 
| Orthologs = {{GNF_Ortholog_box
 
    | Hs_EntrezGene = 3567
 
    | Hs_Ensembl = ENSG00000113525
 
    | Hs_RefseqProtein = NP_000870
 
    | Hs_RefseqmRNA = NM_000879
 
    | Hs_GenLoc_db = 
 
    | Hs_GenLoc_chr = 5
 
    | Hs_GenLoc_start = 131905035
 
    | Hs_GenLoc_end = 131907113
 
    | Hs_Uniprot = P05113
 
    | Mm_EntrezGene = 16191
 
    | Mm_Ensembl = ENSMUSG00000036117
 
    | Mm_RefseqmRNA = NM_010558
 
    | Mm_RefseqProtein = NP_034688
 
    | Mm_GenLoc_db = 
 
    | Mm_GenLoc_chr = 11
 
    | Mm_GenLoc_start = 53564217
 
    | Mm_GenLoc_end = 53568526
 
    | Mm_Uniprot = Q05A89
 
  }}
 
}}
 
'''Interleukin 5''' or '''IL-5''' is an [[interleukin]] produced by [[T helper cell|T helper]]-2 cells and [[mast cells]]. Its functions are to stimulate [[B cell]] growth and increase [[immunoglobulin]] secretion.  It is also a key mediator in [[eosinophil]] activation.  IL-5 is a 115 [[amino acid]] (in man, 133 in the mouse) long TH2 [[cytokine]] which is part of the hematopoietic family.  Unlike other members of this [[cytokine]] family (namely [[Interleukin 3|IL-3]] and [[GM-CSF]]) , in its active form, this glycoprotein is a homodimer <ref>Milburn MV, Hassell AM, Lambert MH, Jordan SR, Proudfoot AE, Graber P et al. A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5. Nature 1993; 363(6425):172-176.</ref>.  The IL-5 [[gene]] is located on [[chromosome]] 11 (in the mouse, chromosome 5 in humans) in close proximity to the genes encoding [[Interleukin 3|IL-3]], [[Interleukin 4|IL-4]] and [[granulocyte-macrophage colony-stimulating factor]] ([[GM-CSF]]) <ref>Lee JS, Campbell HD, Kozak CA, Young IG. The IL-4 and IL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11. Somat Cell Mol Genet 1989; 15(2):143-152.</ref><ref>van Leeuwen BH, Martinson ME, Webb GC, Young IG. Molecular organization of the cytokine gene cluster, involving the human IL-3, IL-4, IL-5, and GM-CSF genes, on human chromosome 5. Blood 1989; 73(5):1142-1148.</ref> which are often co-expressed in TH2 cells.  Interleukin-5 is also expressed by [[eosinophils]] <ref>Dubucquoi S, Desreumaux P, Janin A, Klein O, Goldman M, Tavernier J et al. Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion. J Exp Med 1994; 179(2):703-708.</ref> and has been observed in the [[mast cells]] of asthmatic airways by [[immunohistochemistry]] <ref>Bradding P, Roberts JA, Britten KM, Montefort S, Djukanovic R, Mueller R et al. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 1994; 10(5):471-480.</ref>.  IL-5 expression is regulated by several [[transcription factors]] including [[GATA-3]] <ref>Kaminuma O, Mori A, Kitamura N, Hashimoto T, Kitamura F, Inokuma S et al. Role of GATA-3 in IL-5 gene transcription by CD4+ T cells of asthmatic patients. Int Arch Allergy Immunol 2005; 137 Suppl 1:55-9. Epub;%2005 Jun 2.:55-59.</ref>.
 
  
==Clinical significance==
+
== Function ==
Interleukin-5 has long been associated with several allergic diseases including [[allergic rhinitis]] and [[asthma]] where a large increase in the number of circulating, airway tissue, and induced [[sputum]] eosinophil numbers have been observed <ref>Shen HH, Ochkur SI, McGarry MP, Crosby JR, Hines EM, Borchers MT et al. A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse. J Immunol 2003; 170(6):3296-3305.</ref>.  Given the high concordance of eosinophils and, particularly, allergic asthma pathology, it has been widely speculated that eosinophils have an important role in the pathology of this disease <ref>Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood 1992; 79(12):3101-3109.</ref>.
 
  
==The IL-5 Receptor==
+
Through binding to the [[interleukin-5 receptor]], interleukin 5 stimulates [[B cell]] growth and increases [[immunoglobulin]] secretion - primarily [[IgA]]. It is also a key mediator in [[eosinophil]] activation.
  
The IL-5 receptor (IL-5R) belongs to the [[type I cytokine receptor]] family and is a heterodimer composed of two [[polypeptide]] chains, one α subunit which binds IL-5 and confers upon the receptor cytokine specificity, and one β subunit which contains the [[signal transduction]] domains.
+
== Structure ==
  
===α-subunit===
+
IL-5 is a 115-[[amino acid]] (in human, 133 in the mouse) -long TH2 [[cytokine]] that is part of the hematopoietic familyUnlike other members of this [[cytokine]] family (namely [[interleukin 3]] and [[GM-CSF]]), this glycoprotein in its active form is a homodimer.<ref name="pmid8483502">{{cite journal | vauthors = Milburn MV, Hassell AM, Lambert MH, Jordan SR, Proudfoot AE, Graber P, Wells TN | title = A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5 | journal = Nature | volume = 363 | issue = 6425 | pages = 172–6  | date = May 1993 | pmid = 8483502 | doi = 10.1038/363172a0 }}</ref>
The IL-5Rα chain is exclusively expressed by eosinophils, some [[basophils]] and murine B1 cells or B cell precursors <ref>Geijsen N, Koenderman L, Coffer PJ. Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF receptor family. Cytokine Growth Factor Rev 2001; 12(1):19-25.</ref>.  Like many other cytokine receptors, [[alternative splicing]] of the α-chain gene results in expression of either a membrane bound or soluble form of the α-chain.  The soluble form does not lead to signal transduction and therefore has an antagonistic effect on IL-5 signaling.  Both monomeric forms of IL-5Rα are low affinity receptors, while dimerization with the β-chain produces a high affinity receptor <ref>Tavernier J, Devos R, Cornelis S, Tuypens T, Van der HJ, Fiers W et al. A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF. Cell 1991; %20;66(6):1175-1184.</ref>In either case, the α-chain exclusively binds IL-5 and the intra-cellular portion of IL-5Rα is associated with [[Janus kinase]] ([[JAK]]) 2, a [[protein tyrosine-kinase]] essential in IL-5 signal transduction <ref>Ogata N, Kouro T, Yamada A, Koike M, Hanai N, Ishikawa T et al. JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation. Blood 1998; 91(7):2264-2271.</ref><ref>Takaki S, Kanazawa H, Shiiba M, Takatsu K. A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction. Mol Cell Biol 1994; 14(11):7404-7413.</ref>.
 
  
===β-subunit===
+
== Tissue expression ==
The β-subunit of the IL-5 receptor is responsible for signal transduction and contains several intracellular signaling domains.  Unlike the α-chain, the β-chain does not bind IL-5, is not specific to this cytokine, and is expressed on practically all [[leukocytes]].  In fact, the β-subunit of the IL-5 receptor is also found in [[Interleukin 3|IL-3]] and [[GM-CSF]] receptors where it is associated the [[IL-3Rα]] and [[GM-CSFRα]] subunits respectively <ref>Martinez-Moczygemba M, Huston DP. Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF. J Allergy Clin Immunol 2003; 112(4):653-665.</ref>.  Therefore it is known as the common β receptor or βc.  Like the IL-5Rα subunit, the β subunit’s [[cytoplasmic]] domain is constitutively associated with [[JAK2]] <ref>Quelle FW, Sato N, Witthuhn BA, Inhorn RC, Eder M, Miyajima A et al. JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. Mol Cell Biol 1994; 14(7):4335-4341.</ref>, as well as [[LYN]]<ref>Li Y, Shen BF, Karanes C, Sensenbrenner L, Chen B. Association between Lyn protein tyrosine kinase (p53/56lyn) and the beta subunit of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors in a GM-CSF-dependent human megakaryocytic leukemia cell line (M-07e). J Immunol 1995; 155(4):2165-2174.</ref>, another tyrosine kinase, which are both essential for IL-5 signal transduction <ref>Sato N, Sakamaki K, Terada N, Arai K, Miyajima A. Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signaling. EMBO J 1993; 12(11):4181-4189.</ref>.
 
  
==Effect of IL-5 on Eosinophils==
+
The IL-5 [[gene]] is located on [[chromosome 11]] in the mouse, and chromosome 5 in humans, in close proximity to the genes encoding [[Interleukin 3|IL-3]], [[Interleukin 4|IL-4]], and [[granulocyte-macrophage colony-stimulating factor]] ([[GM-CSF]]),<ref name="pmid2784591">{{cite journal | vauthors = Lee JS, Campbell HD, Kozak CA, Young IG | title = The IL-4 and IL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11 | journal = Somat. Cell Mol. Genet. | volume = 15 | issue = 2 | pages = 143–52  | date = March 1989 | pmid = 2784591 | doi = 10.1007/BF01535075 }}</ref><ref name="pmid2564789">{{cite journal | vauthors = van Leeuwen BH, Martinson ME, Webb GC, Young IG | title = Molecular organization of the cytokine gene cluster, involving the human IL-3, IL-4, IL-5, and GM-CSF genes, on human chromosome 5 | journal = Blood | volume = 73 | issue = 5 | pages = 1142–8  | date = April 1989 | pmid = 2564789 | doi =  }}</ref> which are often co-expressed in TH2 cells.  Interleukin-5 is also expressed by [[eosinophils]]<ref name="pmid8294877">{{cite journal | vauthors = Dubucquoi S, Desreumaux P, Janin A, Klein O, Goldman M, Tavernier J, Capron A, Capron M | title = Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion | journal = J. Exp. Med. | volume = 179 | issue = 2 | pages = 703–8  | date = February 1994 | pmid = 8294877 | pmc = 2191391 | doi = 10.1084/jem.179.2.703 }}</ref> and has been observed in the [[mast cells]] of asthmatic airways by [[immunohistochemistry]].<ref name="pmid8179909">{{cite journal | vauthors = Bradding P, Roberts JA, Britten KM, Montefort S, Djukanovic R, Mueller R, Heusser CH, Howarth PH, Holgate ST | title = Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines | journal = Am. J. Respir. Cell Mol. Biol. | volume = 10 | issue = 5 | pages = 471–80  | date = May 1994 | pmid = 8179909 | doi = 10.1165/ajrcmb.10.5.8179909 }}</ref> IL-5 expression is regulated by several [[transcription factors]] including [[GATA3]].<ref name="pmid15947486">{{cite journal | vauthors = Kaminuma O, Mori A, Kitamura N, Hashimoto T, Kitamura F, Inokuma S, Miyatake S | title = Role of GATA-3 in IL-5 gene transcription by CD4+ T cells of asthmatic patients | journal = Int. Arch. Allergy Immunol. | volume = 137 Suppl 1 | issue =  | pages = 55–9 | year = 2005 | pmid = 15947486 | doi = 10.1159/000085433 }}</ref>
Eosinophils are [[terminally differentiated]] [[granulocytes]] found in most [[mammals]]. The principal role of these cells, in a healthy host, is the elimination of antibody bound parasites through the release of [[cytotoxic]] granule proteins <ref>Giembycz MA, Lindsay MA. Pharmacology of the eosinophil. Pharmacol Rev 1999; 51(2):213-340.</ref>. Given that eosinophils are the primary IL-5Rα expressing cells, it is not surprising that this cell type responds to IL-5.  In fact, IL-5 was originally discovered as an eosinophil colony stimulating factor <ref>Lopez AF, Begley CG, Williamson DJ, Warren DJ, Vadas MA, Sanderson CJ. Murine eosinophil differentiation factor. An eosinophil-specific colony-stimulating factor with activity for human cells. J Exp Med 1986; 163(5):1085-1099.</ref>, is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior at every stage from maturation to survival.
+
 
 +
== Clinical significance ==
 +
 
 +
Interleukin-5 has long been associated with the cause of several allergic diseases including [[allergic rhinitis]] and [[asthma]], wherein a large increase in the number of circulating, airway tissue, and induced [[sputum]] eosinophils have been observed.<ref name="pmid12626589">{{cite journal | vauthors = Shen HH, Ochkur SI, McGarry MP, Crosby JR, Hines EM, Borchers MT, Wang H, Biechelle TL, O'Neill KR, Ansay TL, Colbert DC, Cormier SA, Justice JP, Lee NA, Lee JJ | title = A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse | journal = J. Immunol. | volume = 170 | issue = 6 | pages = 3296–305  | date = March 2003 | pmid = 12626589 | doi = 10.4049/jimmunol.170.6.3296 }}</ref>  Given the high concordance of eosinophils and, in particular, allergic asthma pathology, it has been widely speculated that eosinophils have an important role in the pathology of this disease.<ref name="pmid1596561">{{cite journal | vauthors = Sanderson CJ | title = Interleukin-5, eosinophils, and disease | journal = Blood | volume = 79 | issue = 12 | pages = 3101–9  | date = June 1992 | pmid = 1596561 | doi = }}</ref>
 +
 
 +
Drugs that target IL-5 are [[mepolizumab]] and [[reslizumab]].
 +
 
 +
== Effect on eosinophils ==
 +
 
 +
Eosinophils are terminally differentiated [[granulocytes]] found in most [[mammals]]. The principal role of these cells, in a healthy host, is the elimination of antibody bound parasites through the release of [[cytotoxic]] granule proteins.<ref name="pmid10353986">{{cite journal | vauthors = Giembycz MA, Lindsay MA | title = Pharmacology of the eosinophil | journal = Pharmacol. Rev. | volume = 51 | issue = 2 | pages = 213–340  | date = June 1999 | pmid = 10353986 | doi =  }}</ref>  Given that eosinophils are the primary IL-5Rα-expressing cells, it is not surprising that this cell type responds to IL-5.  In fact, IL-5 was originally discovered as an eosinophil colony-stimulating factor,<ref name="pmid3486243">{{cite journal | vauthors = Lopez AF, Begley CG, Williamson DJ, Warren DJ, Vadas MA, Sanderson CJ | title = Murine eosinophil differentiation factor. An eosinophil-specific colony-stimulating factor with activity for human cells | journal = J. Exp. Med. | volume = 163 | issue = 5 | pages = 1085–99  | date = May 1986 | pmid = 3486243 | pmc = 2188112 | doi = 10.1084/jem.163.5.1085 }}</ref> is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior at every stage from maturation to survival. [[Mepolizumab]] is a monoclonal antibody against IL-5 which can reduce excessive eosinophilia.
 +
 
 +
In [[Hodgkin's Lymphoma|Hodgkin lymphoma]], for instance, the typically-observed [[eosinophilia]] is thought to be attributable to an increased production of IL-5.<ref name="Di Biagio">{{cite journal | vauthors = Di Biagio E, Sánchez-Borges M, Desenne JJ, Suárez-Chacón R, Somoza R, Acquatella G | title = Eosinophilia in Hodgkin's disease: a role for interleukin 5 | journal = Int. Arch. Allergy Immunol. | volume = 110 | issue = 3 | pages = 244–51  | date = Jul 1996 | pmid = 8688671 | doi = 10.1159/000237294 }}</ref>
 +
 
 +
== Interactions ==
 +
 
 +
Interleukin 5 has been shown to [[Protein-protein interaction|interact]] with [[Interleukin 5 receptor alpha subunit]].<ref name="pmid7957082">{{cite journal | vauthors = Woodcock JM, Zacharakis B, Plaetinck G, Bagley CJ, Qiyu S, Hercus TR, Tavernier J, Lopez AF | title = Three residues in the common beta chain of the human GM-CSF, IL-3 and IL-5 receptors are essential for GM-CSF and IL-5 but not IL-3 high affinity binding and interact with Glu21 of GM-CSF | journal = EMBO J. | volume = 13 | issue = 21 | pages = 5176–85  | date = November 1994 | pmid = 7957082 | pmc = 395466 | doi =  }}</ref><ref name="pmid7721873">{{cite journal | vauthors = Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R | title = Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins | journal = J. Biol. Chem. | volume = 270 | issue = 16 | pages = 9459–71  | date = April 1995 | pmid = 7721873 | doi = 10.1074/jbc.270.16.9459 }}</ref><ref name="pmid1732409">{{cite journal | vauthors = Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga A, Takatsu K | title = Molecular cloning and expression of the human interleukin 5 receptor | journal = J. Exp. Med. | volume = 175 | issue = 2 | pages = 341–51  | date = February 1992 | pmid = 1732409 | pmc = 2119102 | doi = 10.1084/jem.175.2.341 }}</ref>
 +
 
 +
== Receptors ==
 +
 
 +
The IL-5 receptor is composed of an α and a βc chain.<ref name="pmid1833065">{{cite journal | vauthors = Tavernier J, Devos R, Cornelis S, Tuypens T, Van der Heyden J, Fiers W, Plaetinck G | title = A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF | journal = Cell | volume = 66 | issue = 6 | pages = 1175–84  | date = September 1991 | pmid = 1833065 | doi = 10.1016/0092-8674(91)90040-6 }}</ref> The α subunit is specific for the IL-5 molecule, whereas the βc subunit also recognised by [[interleukin 3]] (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF).<ref name="pmid1833065"/><ref name="pmid8496674">{{cite journal | vauthors = Takaki S, Murata Y, Kitamura T, Miyajima A, Tominaga A, Takatsu K | title = Reconstitution of the functional receptors for murine and human interleukin 5 | journal = J. Exp. Med. | volume = 177 | issue = 6 | pages = 1523–9  | date = June 1993 | pmid = 8496674 | pmc = 2191058 | doi = 10.1084/jem.177.6.1523 }}</ref> Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.<ref name="pmid21770429">{{cite journal | vauthors = Ishino T, Economou NJ, McFadden K, Zaks-Zilberman M, Jost M, Baxter S, Contarino MR, Harrington AE, Loll PJ, Pasut G, Lievens S, Tavernier J, Chaiken I | title = A protein engineering approach differentiates the functional importance of carbohydrate moieties of interleukin-5 receptor α | journal = Biochemistry | volume = 50 | issue = 35 | pages = 7546–56  | date = September 2011 | pmid = 21770429 | doi = 10.1021/bi2009135 }}</ref>
  
 
== References ==
 
== References ==
 
{{Reflist|2}}
 
{{Reflist|2}}
  
{{interleukins}}
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{{PDB_Gallery|geneid=3567}}
[[pl:Interleukina 5]]
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{{Interleukins}}
[[sr:Интерлеукин 5]]
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{{Interleukin receptor modulators}}
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[[Category:Interleukins]]

Latest revision as of 06:02, 18 September 2018

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Interleukin 5 (IL5) is an interleukin produced by type-2 T helper cells and mast cells.

Function

Through binding to the interleukin-5 receptor, interleukin 5 stimulates B cell growth and increases immunoglobulin secretion - primarily IgA. It is also a key mediator in eosinophil activation.

Structure

IL-5 is a 115-amino acid (in human, 133 in the mouse) -long TH2 cytokine that is part of the hematopoietic family. Unlike other members of this cytokine family (namely interleukin 3 and GM-CSF), this glycoprotein in its active form is a homodimer.[1]

Tissue expression

The IL-5 gene is located on chromosome 11 in the mouse, and chromosome 5 in humans, in close proximity to the genes encoding IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF),[2][3] which are often co-expressed in TH2 cells. Interleukin-5 is also expressed by eosinophils[4] and has been observed in the mast cells of asthmatic airways by immunohistochemistry.[5] IL-5 expression is regulated by several transcription factors including GATA3.[6]

Clinical significance

Interleukin-5 has long been associated with the cause of several allergic diseases including allergic rhinitis and asthma, wherein a large increase in the number of circulating, airway tissue, and induced sputum eosinophils have been observed.[7] Given the high concordance of eosinophils and, in particular, allergic asthma pathology, it has been widely speculated that eosinophils have an important role in the pathology of this disease.[8]

Drugs that target IL-5 are mepolizumab and reslizumab.

Effect on eosinophils

Eosinophils are terminally differentiated granulocytes found in most mammals. The principal role of these cells, in a healthy host, is the elimination of antibody bound parasites through the release of cytotoxic granule proteins.[9] Given that eosinophils are the primary IL-5Rα-expressing cells, it is not surprising that this cell type responds to IL-5. In fact, IL-5 was originally discovered as an eosinophil colony-stimulating factor,[10] is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior at every stage from maturation to survival. Mepolizumab is a monoclonal antibody against IL-5 which can reduce excessive eosinophilia.

In Hodgkin lymphoma, for instance, the typically-observed eosinophilia is thought to be attributable to an increased production of IL-5.[11]

Interactions

Interleukin 5 has been shown to interact with Interleukin 5 receptor alpha subunit.[12][13][14]

Receptors

The IL-5 receptor is composed of an α and a βc chain.[15] The α subunit is specific for the IL-5 molecule, whereas the βc subunit also recognised by interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF).[15][16] Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.[17]

References

  1. Milburn MV, Hassell AM, Lambert MH, Jordan SR, Proudfoot AE, Graber P, Wells TN (May 1993). "A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5". Nature. 363 (6425): 172–6. doi:10.1038/363172a0. PMID 8483502.
  2. Lee JS, Campbell HD, Kozak CA, Young IG (March 1989). "The IL-4 and IL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11". Somat. Cell Mol. Genet. 15 (2): 143–52. doi:10.1007/BF01535075. PMID 2784591.
  3. van Leeuwen BH, Martinson ME, Webb GC, Young IG (April 1989). "Molecular organization of the cytokine gene cluster, involving the human IL-3, IL-4, IL-5, and GM-CSF genes, on human chromosome 5". Blood. 73 (5): 1142–8. PMID 2564789.
  4. Dubucquoi S, Desreumaux P, Janin A, Klein O, Goldman M, Tavernier J, Capron A, Capron M (February 1994). "Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion". J. Exp. Med. 179 (2): 703–8. doi:10.1084/jem.179.2.703. PMC 2191391. PMID 8294877.
  5. Bradding P, Roberts JA, Britten KM, Montefort S, Djukanovic R, Mueller R, Heusser CH, Howarth PH, Holgate ST (May 1994). "Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines". Am. J. Respir. Cell Mol. Biol. 10 (5): 471–80. doi:10.1165/ajrcmb.10.5.8179909. PMID 8179909.
  6. Kaminuma O, Mori A, Kitamura N, Hashimoto T, Kitamura F, Inokuma S, Miyatake S (2005). "Role of GATA-3 in IL-5 gene transcription by CD4+ T cells of asthmatic patients". Int. Arch. Allergy Immunol. 137 Suppl 1: 55–9. doi:10.1159/000085433. PMID 15947486.
  7. Shen HH, Ochkur SI, McGarry MP, Crosby JR, Hines EM, Borchers MT, Wang H, Biechelle TL, O'Neill KR, Ansay TL, Colbert DC, Cormier SA, Justice JP, Lee NA, Lee JJ (March 2003). "A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse". J. Immunol. 170 (6): 3296–305. doi:10.4049/jimmunol.170.6.3296. PMID 12626589.
  8. Sanderson CJ (June 1992). "Interleukin-5, eosinophils, and disease". Blood. 79 (12): 3101–9. PMID 1596561.
  9. Giembycz MA, Lindsay MA (June 1999). "Pharmacology of the eosinophil". Pharmacol. Rev. 51 (2): 213–340. PMID 10353986.
  10. Lopez AF, Begley CG, Williamson DJ, Warren DJ, Vadas MA, Sanderson CJ (May 1986). "Murine eosinophil differentiation factor. An eosinophil-specific colony-stimulating factor with activity for human cells". J. Exp. Med. 163 (5): 1085–99. doi:10.1084/jem.163.5.1085. PMC 2188112. PMID 3486243.
  11. Di Biagio E, Sánchez-Borges M, Desenne JJ, Suárez-Chacón R, Somoza R, Acquatella G (Jul 1996). "Eosinophilia in Hodgkin's disease: a role for interleukin 5". Int. Arch. Allergy Immunol. 110 (3): 244–51. doi:10.1159/000237294. PMID 8688671.
  12. Woodcock JM, Zacharakis B, Plaetinck G, Bagley CJ, Qiyu S, Hercus TR, Tavernier J, Lopez AF (November 1994). "Three residues in the common beta chain of the human GM-CSF, IL-3 and IL-5 receptors are essential for GM-CSF and IL-5 but not IL-3 high affinity binding and interact with Glu21 of GM-CSF". EMBO J. 13 (21): 5176–85. PMC 395466. PMID 7957082.
  13. Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R (April 1995). "Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins". J. Biol. Chem. 270 (16): 9459–71. doi:10.1074/jbc.270.16.9459. PMID 7721873.
  14. Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga A, Takatsu K (February 1992). "Molecular cloning and expression of the human interleukin 5 receptor". J. Exp. Med. 175 (2): 341–51. doi:10.1084/jem.175.2.341. PMC 2119102. PMID 1732409.
  15. 15.0 15.1 Tavernier J, Devos R, Cornelis S, Tuypens T, Van der Heyden J, Fiers W, Plaetinck G (September 1991). "A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF". Cell. 66 (6): 1175–84. doi:10.1016/0092-8674(91)90040-6. PMID 1833065.
  16. Takaki S, Murata Y, Kitamura T, Miyajima A, Tominaga A, Takatsu K (June 1993). "Reconstitution of the functional receptors for murine and human interleukin 5". J. Exp. Med. 177 (6): 1523–9. doi:10.1084/jem.177.6.1523. PMC 2191058. PMID 8496674.
  17. Ishino T, Economou NJ, McFadden K, Zaks-Zilberman M, Jost M, Baxter S, Contarino MR, Harrington AE, Loll PJ, Pasut G, Lievens S, Tavernier J, Chaiken I (September 2011). "A protein engineering approach differentiates the functional importance of carbohydrate moieties of interleukin-5 receptor α". Biochemistry. 50 (35): 7546–56. doi:10.1021/bi2009135. PMID 21770429.

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