HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats.
HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats.
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DOI：
10.1002/art.24763
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发表时间：
2009-09
影响因子：
--
通讯作者：
Colbert, Robert A.
中科院分区：
文献类型：
--
作者：
Delay, Monica L.;Turner, Matthew J.;Klenk, Erin I.;Smith, Judith A.;Sowders, Dawn P.;Colbert, Robert A.
To determine whether HLA-B27 misfolding and the unfolded protein response (UPR) results in cytokine dysregulation, and whether this is associated with Th1 and/or Th17 activation in HLA-B27/human beta-2-microglobulin (hβ2m) transgenic rats (HLA-B27 transgenic), an animal model of spondyloarthropathy. Cytokine expression in LPS-stimulated macrophages was analyzed in the presence and absence of a UPR induced by chemical agents or HLA-B27 upregulation. Cytokine expression in colon tissue and in cells purified from the lamina propria was determined by real time reverse-transcriptase polymerase chain reaction, and differences in Th1 and Th17 CD4+ T cell populations were quantified with intracellular cytokine staining. IL-23 was found to be synergistically upregulated by LPS in macrophages undergoing a UPR induced either by pharmacologic agents or HLA-B27 misfolding. IL-23 was also increased in the colon of HLA-B27 transgenic rats concurrent with the development of intestinal inflammation, and IL-17, a downstream target of IL-23, exhibited robust upregulation in a similar temporal pattern. IL-23 and IL-17 transcripts were localized to CD11+ antigen presenting cells and CD4+ T cells, respectively, from the colonic lamina propria. Colitis was associated with a 6-fold expansion of CD4+ IL-17-expressing T cells. The IL-23/IL-17 axis is strongly activated in the colon of HLA-B27 transgenic rats with spondyloarthropathy-like disease. HLA-B27 misfolding and UPR activation in macrophages can result in enhanced induction of the pro-Th17 cytokine, IL-23. These results suggest a possible link between HLA-B27 misfolding and immune dysregulation in this animal model with implications for human disease.
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DOI：
10.4049/jimmunol.181.7.4733
发表时间：
2008-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kryczek I;Bruce AT;Gudjonsson JE;Johnston A;Aphale A;Vatan L;Szeliga W;Wang Y;Liu Y;Welling TH;Elder JT;Zou W
通讯作者：
Zou W
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
--
作者：
Chu, Cong-Qiu;Swart, David;Elkon, Keith B.
通讯作者：
Elkon, Keith B.
影响因子：
4.8
作者：
Antoniou, AN;Ford, S;Powis, SJ
通讯作者：
Powis, SJ