Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis.
Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis.
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DOI：
10.1038/s41467-017-01771-2
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发表时间：
2017-11-15
影响因子：
16.6
通讯作者：
Bowness P
中科院分区：
文献类型：
--
作者：
Al-Mossawi MH;Chen L;Fang H;Ridley A;de Wit J;Yager N;Hammitzsch A;Pulyakhina I;Fairfax BP;Simone D;Yi Y;Bandyopadhyay S;Doig K;Gundle R;Kendrick B;Powrie F;Knight JC;Bowness P
脊柱炎包括一组常见的炎性疾病，被认为是由分泌il - 17a的17型淋巴细胞驱动的。我们发现脊柱炎患者血液和关节中产生GM-CSF的CD4和CD8淋巴细胞数量增加，IL-17A+GM-CSF+双重产生CD4、CD8、γδ和NK细胞数量增加。CD4 T细胞中GM-CSF的产生既可以独立发生，也可以与经典Th1和Th17细胞因子联合发生。主要产生GM-CSF的3型先天淋巴样细胞在脊椎关节炎患者的滑膜组织中扩增。使用三重细胞因子捕获方法分离的GM-CSF+CD4+细胞具有特定的转录特征。在全基因组关联研究和小鼠炎症疾病模型的致病性中，GM-CSF+和IL-17A+GM-CSF+双产CD4 T细胞表达GPR65水平升高，GPR65是一种与脊椎关节炎相关的质子感应受体。沉默原代CD4 T细胞中的GPR65可减少GM-CSF的产生。因此，GM-CSF和GPR65可能作为脊柱炎治疗干预的靶点。脊柱炎是一种炎症性疾病，Th17细胞参与其发病机制。在这里，作者表明，脊柱炎患者分泌gm - csf的血液和滑膜淋巴细胞数量增加，Th17与否，携带独特的转录谱，包括增强的GPR65表达。
Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF-producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A+GM-CSF+ double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF+CD4+ cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF+ and IL-17A+GM-CSF+ double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis. Spondyloarthritis is an inflammatory disease with Th17 cells implicated in the pathogenesis. Here the authors show that patients with spondyloarthritis have increased numbers of GM-CSF-secreting blood and synovial lymphocytes, Th17 or not, that carry a unique transcriptional profile including enhanced GPR65 expression.
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MOR103，一种对粒细胞巨噬细胞刺激因子的人类单克隆抗体，用于治疗中等类风湿关节炎患者：IB/IIA期随机，双盲，安慰剂对照，剂量 - 剂量 - 降低试验的结果。
影响因子：
27.4
作者：
Behrens F;Tak PP;Østergaard M;Stoilov R;Wiland P;Huizinga TW;Berenfus VY;Vladeva S;Rech J;Rubbert-Roth A;Korkosz M;Rekalov D;Zupanets IA;Ejbjerg BJ;Geiseler J;Fresenius J;Korolkiewicz RP;Schottelius AJ;Burkhardt H
通讯作者：
Burkhardt H
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
158.5
作者：
Baeten, Dominique;Sieper, Joachim;Richards, Hanno B.
通讯作者：
Richards, Hanno B.
影响因子：
30.8
作者：
Ellinghaus D;Jostins L;Spain SL;Cortes A;Bethune J;Han B;Park YR;Raychaudhuri S;Pouget JG;Hübenthal M;Folseraas T;Wang Y;Esko T;Metspalu A;Westra HJ;Franke L;Pers TH;Weersma RK;Collij V;D'Amato M;Halfvarson J;Jensen AB;Lieb W;Degenhardt F;Forstner AJ;Hofmann A;International IBD Genetics Consortium (IIBDGC);International Genetics of Ankylosing Spondylitis Consortium (IGAS);International PSC Study Group (IPSCSG);Genetic Analysis of Psoriasis Consortium (GAPC);Psoriasis Association Genetics Extension (PAGE);Schreiber S;Mrowietz U;Juran BD;Lazaridis KN;Brunak S;Dale AM;Trembath RC;Weidinger S;Weichenthal M;Ellinghaus E;Elder JT;Barker JN;Andreassen OA;McGovern DP;Karlsen TH;Barrett JC;Parkes M;Brown MA;Franke A
通讯作者：
Franke A
影响因子：
5.5
作者：
Brandt, J;Listing, J;Braun, J
通讯作者：
Braun, J