The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Identification of Functional Roles for Both IL-17RB and IL-17RA in Mediating IL-25-Induced Activities
Open accessAbstract
IL-25 (IL-17E) is a unique IL-17 family ligand that promotes Th2-skewed inflammatory responses. Intranasal administration of IL-25 into naive mice induces pulmonary inflammation similar to that seen in patients with allergic asthma, including increases in bronchoalveolar lavage fluid eosinophils, bronchoalveolar lavage fluid IL-5 and IL-13 concentrations, goblet cell hyperplasia, and increased airway hyperresponsiveness. IL-25 has been reported to bind and signal through IL-17RB (IL-17BR, IL-17Rh1). It has been demonstrated recently that IL-17A signals through a heteromeric receptor composed of IL-17RA and IL-17RC. We sought to determine whether other IL-17 family ligands also utilize heteromeric receptor complexes. The required receptor subunits for IL-25 biological activities were investigated in vitro and in vivo using a combination of knockout (KO) mice and antagonistic Abs. Unlike wild-type mice, cultured splenocytes from either IL-17RB KO or IL-17RA KO mice did not produce IL-5 or IL-13 in response to IL-25 stimulation, and both IL-17RB KO and IL-17RA KO mice did not respond to intranasal administration of IL-25. Furthermore, treatment with antagonistic mAbs to either IL-17RB or IL-17RA completely blocked IL-25-induced pulmonary inflammation and airway hyperresponsiveness in naive BALB/c mice, similar to the effects of an antagonistic Ab to IL-25. Finally, a blocking Ab to human IL-17RA prevented IL-25 activity in a primary human cell-based assay. These data demonstrate for the first time that IL-25-mediated activities require both IL-17RB and IL-17RA and provide another example of an IL-17 family ligand that utilizes a heteromeric receptor complex.
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Citations
Cites
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Self-citationIL-17E, a Novel Proinflammatory Ligand for the IL-17 Receptor Homolog IL-17Rh1
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Cited by
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Interleukin-17 and Type 17 Helper T Cells
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Metadata
- Authors
- Rickel, E. A., Siegel, L. A., Yoon, B.-R. P., Rottman, J. B., Kugler, D. G., Swart, D. A., Anders, P. M., Tocker, J. E., Comeau, M. R., & Budelsky, A. L.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-09
- Volume
- 181
- Issue
- 6
- Pages
- 4299-4310
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1805155421
- Cited by
- 321
- References
- 29
- FWCI
- 12.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Rickel, E. A., Siegel, L. A., Yoon, B.-R. P., Rottman, J. B., Kugler, D. G., Swart, D. A., Anders, P. M., Tocker, J. E., Comeau, M. R., & Budelsky, A. L. (2008). Identification of Functional Roles for Both IL-17RB and IL-17RA in Mediating IL-25-Induced Activities. The Journal of Immunology. https://doi.org/10.4049/jimmunol.181.6.4299
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