Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation.
Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation.
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DOI：
10.1136/annrheumdis-2012-202925
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发表时间：
2014-08
影响因子：
27.4
通讯作者：
Triolo G
中科院分区：
文献类型：
--
作者：
Ciccia F;Accardo-Palumbo A;Rizzo A;Guggino G;Raimondo S;Giardina A;Cannizzaro A;Colbert RA;Alessandro R;Triolo G
IL-23与强直性脊柱炎（AS）的发病机制有关。本研究的目的是阐明AS患者肠道中IL-23表达增加的机制。收集HLA-B_（27）阳性AS患者30例、克罗恩病（CD）患者15例和正常对照者10例。研究了HLA-B27错误折叠的证据。通过RT-PCR和免疫组织化学评估未折叠蛋白反应（UPR）和自噬。UPR和自噬在IL-23表达调节中的贡献在分离的固有层单核细胞（LPMC）的体外实验中进行了评估。在AS患者的肠道中观察到SYVN 1和FHC的细胞内共定位，但未观察到UPR基因的显著过表达。相反，在AS和CD患者的肠道中观察到参与自噬途径的基因的上调。免疫组化显示AS和CD患者回肠中LC 3 II、ATG 5和ATG 12的表达增加，但SQSTM 1的表达不增加。LC 3 II在AS和CD中表达于浸润的单个核细胞和类似潘氏细胞的上皮细胞中，并与ATG 5共定位。自噬而非UPR是调节慢性肠道炎症AS患者、CD患者和对照组的分离LPMC中IL-23表达所必需的。我们的数据表明，HLA-B27错误折叠发生在AS患者的肠道中，并伴随着自噬的激活，而不是未折叠的蛋白质反应。自噬似乎与AS中IL-23的肠道调节有关。
IL-23 has been implicated in the pathogenesis of Ankylosing Spondylitis (AS). Aim of the study was to clarify the mechanisms underlying the increased IL-23 expression in the gut of AS patients. Consecutive gut biopsies from 30 HLA-B27+ AS patients, 15 Crohn’s disease (CD) patients and 10 normal subjects were obtained. Evidence for HLA-B27 misfolding was studied. Unfolded protein response (UPR) and autophagy were assessed by rt-PCR and immunohistochemistry. The contribution of UPR and autophagy in the regulation of IL-23 expression was evaluated in in vitro experiments on isolated lamina propria mononuclear cells (LPMCs). Intracellular co-localization of SYVN1 and FHCs but not a significant over-expression of UPR genes was observed in the gut of AS patients. Conversely, up-regulation of the genes involved in the autophagy pathway was observed in the gut of AS and CD patients. Immunohistochemistry showed an increased expression of LC3II, ATG5 and ATG12 but not of SQSTM1 in the ileum of AS and CD patients. LC3II was expressed among infiltrating mononuclear cells and epithelial cells resembling Paneth cells and co-localized with ATG5 in AS and CD. Autophagy but not UPR was required to modulate the expression of IL-23 in isolated LPMCs of AS patients with chronic gut inflammation, CD patients and controls. Our data suggest that HLA-B27 misfolding occurs in the gut of AS patients and is accompanied by activation of autophagy rather than an unfolded protein response. Autophagy appears to be associated with intestinal modulation of IL-23 in AS.
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影响因子：
15.9
作者：
Becker, C;Wirtz, S;Neurath, MF
通讯作者：
Neurath, MF
影响因子：
29.4
作者：
Diehl JA;Fuchs SY;Koumenis C
通讯作者：
Koumenis C
影响因子：
--
作者：
Ciccia, Francesco;Accardo-Palumbo, Antonina;Triolo, Giovanni
通讯作者：
Triolo, Giovanni
DOI：
10.1073/pnas.1011736107
发表时间：
2010-10-12
影响因子：
11.1
作者：
Goodall, Jane C.;Wu, Changxin;Gaston, J. S. Hill
通讯作者：
Gaston, J. S. Hill
影响因子：
3.7
作者：
Bogaert S;De Vos M;Olievier K;Peeters H;Elewaut D;Lambrecht B;Pouliot P;Laukens D
通讯作者：
Laukens D