Rheumatoid arthritis patients exhibit impaired Candida albicans-specific Th17 responses.
Rheumatoid arthritis patients exhibit impaired Candida albicans-specific Th17 responses.
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DOI：
10.1186/ar4480
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发表时间：
2014-02-11
影响因子：
4.9
通讯作者：
Levesque MC
中科院分区：
文献类型：
--
作者：
Bishu S;Su EW;Wilkerson ER;Reckley KA;Jones DM;McGeachy MJ;Gaffen SL;Levesque MC
大量资料表明，类风湿关节炎（RA）与CD 4 + T细胞亚群（Th 17细胞）有关。IL-17是诱导肿瘤坏死因子（TNF）α、IL-1β和IL-6的炎性细胞因子，所有这些都是用于治疗RA的生物疗法的靶点。RA患者比年龄匹配的对照组经历更多的感染，生物治疗进一步增加了感染的风险。Th 17/IL-17轴对于对真菌的免疫至关重要，特别是真菌白色念珠菌。因此，我们有必要研究RA与C易感性的关系。白念珠菌，因为越来越多的兴趣在Th 17细胞和IL-17驱动自身免疫，和新的生物制剂的出现，靶向这一途径。我们分析了48例RA和33例健康对照者的外周血和唾液。对C.白念珠菌特异性Th 17应答，将PBMC与热灭活的C.白色念珠菌提取物，并通过ELISA测量条件化上清液中的IL-17 A水平。用流式细胞仪检测Th 17和Th 1细胞的频率。作为IL-17 A介导的效应反应的量度，我们评估了C.口腔中的白色念珠菌定植率、唾液杀真菌活性和唾液中抗菌肽β-防御素2（BD 2）的水平。与对照组相比，来自RA受试者的PBMC表现出升高的IL-17 A基线产生（P = 0.004），尽管它们响应于Th 17细胞分化细胞因子具有相似的产生IL-17 A的能力（P = 0.91）。然而，RA PBMC对C.白念珠菌抗原（P = 0.006）。显著更多的RA患者被C.口腔内白色念珠菌的检出率明显高于健康人（P = 0.02）。同时，RA唾液中的唾液BD 2浓度降低（P = 0.02）。尽管如此，唾液的杀真菌活性在RA受试者中得以保留（P = 0.70）。类风湿关节炎受试者表现出可检测的口腔免疫反应的损害，C。白色念珠菌，一种强烈的Th 17依赖性机会性病原体，尽管IL-17 A的基线产生总体升高。
Accumulating data implicate the CD4+ T cell subset (Th17 cells) in rheumatoid arthritis (RA). IL-17 is an inflammatory cytokine that induces tumor necrosis factor (TNF)α, IL-1β and IL-6, all of which are targets of biologic therapies used to treat RA. RA patients are well documented to experience more infections than age-matched controls, and biologic therapies further increase the risk of infection. The Th17/IL-17 axis is vital for immunity to fungi, especially the commensal fungus Candida albicans. Therefore, we were prompted to examine the relationship between RA and susceptibility to C. albicans because of the increasing interest in Th17 cells and IL-17 in driving autoimmunity, and the advent of new biologics that target this pathway. We analyzed peripheral blood and saliva from 48 RA and 33 healthy control subjects. To assess C. albicans-specific Th17 responses, PBMCs were co-cultured with heat-killed C. albicans extract, and IL-17A levels in conditioned supernatants were measured by ELISA. The frequency of Th17 and Th1 cells was determined by flow cytometry. As a measure of IL-17A-mediated effector responses, we evaluated C. albicans colonization rates in the oral cavity, salivary fungicidal activity and levels of the antimicrobial peptide β-defensin 2 (BD2) in saliva. Compared to controls, PBMCs from RA subjects exhibited elevated baseline production of IL-17A (P = 0.004), although they had similar capacity to produce IL-17A in response to Th17 cell differentiating cytokines (P = 0.91). However RA PBMCs secreted less IL-17A in response to C. albicans antigens (P = 0.006). Significantly more RA patients were colonized with C. albicans in the oral cavity than healthy subjects (P = 0.02). Concomitantly, RA saliva had reduced concentrations of salivary BD2 (P = 0.02). Nonetheless, salivary fungicidal activity was preserved in RA subjects (P = 0.70). RA subjects exhibit detectable impairments in oral immune responses to C. albicans, a strongly Th17-dependent opportunistic pathogen, despite an overall elevated baseline production of IL-17A.
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影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
30.8
作者：
Eyre, Steve;Bowes, John;Diogo, Dorothee;Lee, Annette;Barton, Anne;Martin, Paul;Zhernakova, Alexandra;Stahl, Eli;Viatte, Sebastien;McAllister, Kate;Amos, Christopher I.;Padyukov, Leonid;Toes, Rene E. M.;Huizinga, Tom W. J.;Wijmenga, Cisca;Trynka, Gosia;Franke, Lude;Westra, Harm-Jan;Alfredsson, Lars;Hu, Xinli;Sandor, Cynthia;de Bakker, Paul I. W.;Davila, Sonia;Khor, Chiea Chuen;Heng, Khai Koon;Andrews, Robert;Edkins, Sarah;Hunt, Sarah E.;Langford, Cordelia;Symmons, Deborah;Concannon, Pat;Onengut-Gumuscu, Suna;Rich, Stephen S.;Deloukas, Panos;Gonzalez-Gay, Miguel A.;Rodriguez-Rodriguez, Luis;Arlsetig, Lisbeth;Martin, Javier;Rantapaa-Dahlqvist, Solbritt;Plenge, Robert M.;Raychaudhuri, Soumya;Klareskog, Lars;Gregersen, Peter K.;Worthington, Jane
通讯作者：
Worthington, Jane
DOI：
10.1038/nri2586
发表时间：
2009-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
30.5
作者：
McGeachy, Mandy J.;Bak-Jensen, Kristian S.;Cua, Daniel J.
通讯作者：
Cua, Daniel J.
影响因子：
3.7
作者：
Marijnissen, Renoud J.;Koenders, Marije I.;van den Berg, Wim B.
通讯作者：
van den Berg, Wim B.