Interleukin-17 as a molecular target in immune-mediated arthritis: Immunoregulatory properties of genetically modified murine dendritic cells that secrete interleukin-4
dc.contributor.author | Sarkar, Sujata | en_US |
dc.contributor.author | Tesmer, Laura A. | en_US |
dc.contributor.author | Hindnavis, Vindhya | en_US |
dc.contributor.author | Endres, Judith L. | en_US |
dc.contributor.author | Fox, David A. | en_US |
dc.date.accessioned | 2007-09-20T18:07:16Z | |
dc.date.available | 2008-04-03T18:48:04Z | en_US |
dc.date.issued | 2007-01 | en_US |
dc.identifier.citation | Sarkar, Sujata; Tesmer, Laura A.; Hindnavis, Vindhya; Endres, Judith L.; Fox, David A. (2007). "Interleukin-17 as a molecular target in immune-mediated arthritis: Immunoregulatory properties of genetically modified murine dendritic cells that secrete interleukin-4." Arthritis & Rheumatism 56(1): 89-100. <http://hdl.handle.net/2027.42/55925> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/55925 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17195211&dopt=citation | en_US |
dc.description.abstract | Objective Our previous studies have shown that murine dendritic cells (DCs) genetically modified to express interleukin-4 (IL-4) reduce the incidence and severity of murine collagen-induced arthritis. The present studies were performed to assess the immunoregulatory mechanisms underlying this response, by assessing the effects of IL-4 DCs on cytokine production by subsets of T helper cells. Methods Male DBA mice ages 6–8 weeks old were immunized with type II collagen. Splenic T cells obtained during the initiation phase and the end stage of arthritis were cultured with IL-4 DCs or untransduced DCs in the presence of collagen rechallenge. Interferon-Γ (IFNΓ) and IL-17 responses were measured. Antibodies to IL-4, IL-12, and IL-23, and recombinant IL-4, IL-12, and IL-23 were used to further study the regulation of T cell cytokine production by IL-4 DCs. Results Splenic T cells obtained during the initiation phase of arthritis produced less IL-17 when cultured in the presence of IL-4 DCs, despite their production of increased quantities of other proinflammatory cytokines (IFNΓ and tumor necrosis factor). T cell IL-17 production after collagen rechallenge was not inhibited by a lack of IL-23, since IL-4–mediated suppression of IL-17 was not reconstituted by IL-23, an otherwise potent inducer of IL-17 production by T cells. Although IL-4 DCs can produce increased quantities of IL-12 and IFNΓ, suppression of IL-17 production by IL-4 DCs was independent of both. While IL-17 production by T cells obtained during the initiation phase of arthritis was regulated by IL-4 DCs, IL-17 production by T cells obtained during end-stage arthritis was not altered. Conclusion Our data suggest that IL-4 DCs exert a therapeutic effect on collagen-induced arthritis by targeting IL-17. IL-17 suppression by IL-4 DCs is robust and is not reversed by IL-23. Timing might be important in IL-17–targeted therapy, since IL-17 production by T cells obtained during end-stage arthritis did not respond to suppression by IL-4 DCs. | en_US |
dc.format.extent | 255077 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | Interleukin-17 as a molecular target in immune-mediated arthritis: Immunoregulatory properties of genetically modified murine dendritic cells that secrete interleukin-4 | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor ; Division of Rheumatology, Room 3918 Taubman Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109 | en_US |
dc.identifier.pmid | 17195211 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/55925/1/22311_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/art.22311 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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