Interleukin 25
| IL25 | |||
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| Location (UCSC) | Chr 14: 23.37 – 23.38 Mb | Chr 14: 55.17 – 55.17 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Interleukin-25 (IL-25) – also known as interleukin-17E (IL-17E)[5] – is a protein that in humans is encoded by the IL25 gene on chromosome 14.[6][7][8] IL-25 was discovered in 2001 and is made up of 177 amino acids.[6]
IL-25 and IL-17 family
IL-25 is a
IL-25 signals through a heterohexameric receptor complex containing IL-17RA and IL-17RB. In this complex, IL-25 forms a homodimer with IL-17RB, which then binds to IL-17RA.[10] The IL-17RA subunit is common for IL-17A and IL-17F, and IL-17RB is common for IL-17B. Both IL-17RA and IL-17RB are essential for IL-25 functions. IL-25 does not bind directly to IL-17RA, but this subunit is necessary for its functions - as well as IL-17RB which directly bind IL-25.[11][12]
Function
IL-25 is produced by many cell types. These cells include T cells, dendritic cells, macrophages, mast cells, basophils, eosinophils, epithelial cells and Paneth cells.[13][14]
This cytokine can induce NF-κB activation, and stimulate the production of IL-8 (named also CXCL8), which is the major chemotactic substance of neutrophils.[6]
Another important function of interleukin 25 is to support the Th2 immune response. IL-25 has been shown to induce the production of IL-4, IL-5 and IL-13.[7] Evidence is the expression of IL-17RB on Th2 cells, not on Th1 and Th17.[15] In addition, IL-25 is responsible for the decrease in IFN gamma.[15][16]
Because IL-25 promotes the development of a Th2 immune response, it acts to protect against several bowel infections caused by helminths.[16][17] This role of IL-25 has been demonstrated in these intestinal parasites - Nippostrongylus brasiliensis [18], Trichuris muris [16], Trichinella spiralis [19] a Heligmosomoides polygyrus bekeri. [17]
IL-25 is also referred to as the regulator of IL-9 production. IL-25 has been shown to increase the production of IL-9 in Th9 cells. Th9 cells can arise not only from naive T cells but also from differentiated Th2 cells.[20]
Another function of IL-25 is the activation of natural lymphoid cells 2 (ILC2). IL-25 and IL-33 are the most potent activators of ILC2.[21][22]
Clinical significance
IL-25 induces the production of other cytokines, including
Further, the IL-25 gene has been identified in a chromosomal region associated with diseases of the gut such as inflammatory bowel disease (IBD), although no direct evidence suggests that IL-25 plays any role in this disease.[24]
IL-25 has potent antitumor activity in vivo in several human cancers including melanoma, breast, lung, colon, and pancreatic cancers, suggesting the potential clinical use of IL-17E as an anticancer agent.[25]
IL-25 and allergy
IL-25 works pathologically in allergies. It is a cytokine that supports the Th2 response. IL-25 induces IL-4, IL-5 a[clarification needed] IL-13, cytokines which play important role in allergies.[7][26]
Many studies suggest that blocking IL-25 activity might be useful in the treatment of allergies. Research studies suggest the blocking of IL-25 activity by the neutralizing antibody against IL-25. A delayed Th2 differentiation and delayed production of cytokines IL-4, IL-5 and IL-13 have been demonstrated in the IL-25 knockout mouse.[18]
IL-25 influences the development of nasal polyps, and may also be involved in the etiology of chronic rhinitis with nasal polyps. A 2018 study found that after using a non-neutralizing antibody against IL-25, IL-4, IL-5, and IL-13 decreased, and the number of nasal polyps decreased.[27]
Another proposed option of treating allergies with IL-25 is a combination of neutralizing antibodies against IL-25, IL-33 and TSLP (thymic stromal lymphopoietin). All three of these cytokines support the Th2 immune response.[28]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000166090 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040770 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Product reference for IL-17E
- ^ PMID 11058597.
- ^ PMID 11754819.
- ^ "Entrez Gene: IL25 interleukin 25".
- PMID 12651226.
- PMID 35863378.
- PMID 18768888.
- PMID 25888259.
- PMID 21349428.
- PMID 23917206.
- ^ PMID 17562814.
- ^ PMID 16606667.
- ^ PMID 27620722.
- ^ PMID 16606668.
- PMID 23897610.
- PMID 20154671.
- S2CID 2228459.
- PMID 20200518.
- PMID 21490275.
- Lay summary in: "Researchers Find Healthy Breast Tissue Secretes IL-25 to Kill Tumor Cells". Genetic Engineering & Biotechnology News. April 14, 2011.
- PMID 14641539.
- S2CID 1895002.
- PMID 26699081.
- PMID 29456832.
- PMID 28552763.
Further reading
- Fallon PG, Ballantyne SJ, Mangan NE, Barlow JL, Dasvarma A, Hewett DR, McIlgorm A, Jolin HE, PMID 16606668.
- Pan G, French D, Mao W, Maruoka M, Risser P, Lee J, Foster J, Aggarwal S, Nicholes K, Guillet S, Schow P, Gurney AL (December 2001). "Forced expression of murine IL-17E induces growth retardation, jaundice, a Th2-biased response, and multiorgan inflammation in mice". Journal of Immunology. 167 (11): 6559–67. PMID 11714825.
- Kim MR, Manoukian R, Yeh R, Silbiger SM, Danilenko DM, Scully S, Sun J, DeRose ML, Stolina M, Chang D, Van GY, Clarkin K, Nguyen HQ, Yu YB, Jing S, Senaldi G, Elliott G, Medlock ES (October 2002). "Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production". Blood. 100 (7): 2330–40. S2CID 253678.
- Zhang Z, Henzel WJ (October 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science. 13 (10): 2819–24. PMID 15340161.
- Létuvé S, Lajoie-Kadoch S, Audusseau S, Rothenberg ME, Fiset PO, Ludwig MS, Hamid Q (March 2006). "IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts". The Journal of Allergy and Clinical Immunology. 117 (3): 590–6. PMID 16522458.
- Tamachi T, Maezawa Y, Ikeda K, Kagami S, Hatano M, Seto Y, Suto A, Suzuki K, Watanabe N, Saito Y, Tokuhisa T, Iwamoto I, Nakajima H (September 2006). "IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice". The Journal of Allergy and Clinical Immunology. 118 (3): 606–14. PMID 16950278.
- Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, Hippe A, Corrigan CJ, Dong C, Homey B, Yao Z, Ying S, Huston DP, Liu YJ (August 2007). "IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells". The Journal of Experimental Medicine. 204 (8): 1837–47. PMID 17635955.