A polymorphism in the interleukin-4 receptor affects the ability of interleukin-4 to regulate Th17 cells: a possible immunoregulatory mechanism for genetic control of the severity of rheumatoid arthritis
dc.contributor.author | Wallis, Susan K. | |
dc.contributor.author | Cooney, Laura A. | |
dc.contributor.author | Endres, Judith L. | |
dc.contributor.author | Lee, Min J. | |
dc.contributor.author | Ryu, Jennifer | |
dc.contributor.author | Somers, Emily C. | |
dc.contributor.author | Fox, David A. | |
dc.date.accessioned | 2015-08-07T17:34:55Z | |
dc.date.available | 2015-08-07T17:34:55Z | |
dc.date.issued | 2011-02-04 | |
dc.identifier.citation | Arthritis Research & Therapy. 2011 Feb 04;13(1):R15 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/112571 | en_US |
dc.description.abstract | Abstract Introduction Rheumatoid arthritis (RA) is now suspected to be driven by pathogenic Th17 cells that secrete interleukin (IL)-17 and can be regulated by IL-4. A single-nucleotide polymorphism (SNP), I50V, in the coding region of the human IL-4 receptor (IL-4R) is associated with rapid development of erosive disease in RA. The present study was undertaken to determine whether this SNP renders the IL-4R less able to transduce signals that regulate IL-17 production. Methods Peripheral blood mononuclear cells were activated under Th17-stimulating conditions in the presence or absence of IL-4, and IL-17 production was measured by both enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Serum IL-17 was also measured by ELISA. Paired comparisons were performed using the two-tailed t-test. IL-4 receptor gene alleles were determined by polymerase chain reaction. Results In healthy individuals, IL-4 significantly inhibited IL-17 production by cells from subjects with the I/I genotype (P = 0.0079) and the I/V genotype (P = 0.013), but not the V/V genotype (P > 0.05). In a cross-sectional sample of patients with established RA, the magnitude of the in vitro effect of IL-4 was lower and was not associated with a specific IL-4R allele. Serum IL-17 levels were higher in RA patients than in healthy individuals, as was the percentage of CD4+ cells that produced IL-17. Conclusions These results indicate that an inherited polymorphism of the IL-4R controls the ability of the human immune system to regulate the magnitude of IL-17 production. However, in established RA, this pattern may be altered, possibly due to secondary effects of both RA itself as well as immunomodulatory medications. Ineffective control of Th17 immune responses is a potential mechanism to explain why IL-4R is an important severity gene in RA, but this issue will require careful study of a cohort of new-onset RA patients. | |
dc.title | A polymorphism in the interleukin-4 receptor affects the ability of interleukin-4 to regulate Th17 cells: a possible immunoregulatory mechanism for genetic control of the severity of rheumatoid arthritis | |
dc.type | Article | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/112571/1/13075_2010_Article_2995.pdf | |
dc.identifier.doi | 10.1186/ar3239 | en_US |
dc.language.rfc3066 | en | |
dc.rights.holder | Wallis et al.; licensee BioMed Central Ltd. | |
dc.date.updated | 2015-08-07T17:34:55Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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