A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis.
A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis.
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DOI：
10.1084/jem.20170412
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发表时间：
2017-11-06
期刊：
影响因子：
--
通讯作者：
Pascual V
中科院分区：
文献类型：
--
作者：
Cepika AM;Banchereau R;Segura E;Ohouo M;Cantarel B;Goller K;Cantrell V;Ruchaud E;Gatewood E;Nguyen P;Gu J;Anguiano E;Zurawski S;Baisch JM;Punaro M;Baldwin N;Obermoser G;Palucka K;Banchereau J;Amigorena S;Pascual V
系统性幼年特发性关节炎自身炎症的病因尚不清楚。Cepka等人。使用多维血液刺激数据的综合分析，应用于停止治疗和完全缓解的患者，以揭示可能易患疾病的潜在细胞和分子机制。散发性人类慢性炎症性疾病的病因大多尚不清楚。为了填补这一空白，我们开发了一种策略，在转录、细胞和分泌蛋白水平上同时整合血液白细胞对天然刺激的反应。当应用于全身性幼年特发性关节炎(SJIA)时，这种方法识别了与特定细胞因子环境和激活的白细胞亚群相关的基因集。在疾病缓解和停药期间，sJIA患者对TLR4、TLR8和TLR7刺激的反应异常。分离的单核细胞在基线水平表达IL-1抑制剂芳烃受体，刺激后细胞内积累较高水平的IL-1β。支持AHR下调使单核细胞向巨噬细胞分化的证据，sJIA单核细胞在体外向巨噬细胞分化，远离树突状细胞表型。这可能是这些患者巨噬细胞激活综合征发生率增加的原因之一。因此，对高维数据的综合分析可以揭开易患复杂炎症性疾病的免疫变化。
The etiology of autoinflammation in systemic juvenile idiopathic arthritis is unclear. Cepika et al. use integrated analysis of multidimensional blood stimulation data, applied to patients while off treatment and in complete remission, to reveal underlying cellular and molecular mechanisms that might predispose to disease. The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During disease remission and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8, and TLR7 stimulation. Isolated sJIA monocytes underexpressed the IL-1 inhibitor aryl hydrocarbon receptor (AHR) at baseline and accumulated higher levels of intracellular IL-1β after stimulation. Supporting the demonstration that AHR down-regulation skews monocytes toward macrophage differentiation, sJIA monocytes differentiated in vitro toward macrophages, away from the dendritic cell phenotype. This might contribute to the increased incidence of macrophage activation syndrome in these patients. Integrated analysis of high-dimensional data can thus unravel immune alterations predisposing to complex inflammatory diseases.
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影响因子：
30.5
作者：
Alsina, Laia;Israelsson, Elisabeth;Altman, Matthew C.;Dang, Kristen K.;Ghandil, Pegah;Israel, Laura;von Bernuth, Horst;Baldwin, Nicole;Qin, Huanying;Jin, Zongbo;Banchereau, Romain;Anguiano, Esperanza;Ionan, Alexei;Abel, Laurent;Puel, Anne;Picard, Capucine;Pascual, Virginia;Casanova, Jean Laurent;Chaussabel, Damien
通讯作者：
Chaussabel, Damien
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
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
5.4
作者：
Chaussabel D;Pascual V;Banchereau J
通讯作者：
Banchereau J
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ