Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis.
Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis.
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DOI：
10.3389/fimmu.2018.00755
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发表时间：
2018
影响因子：
7.3
通讯作者：
Isaacs JD
中科院分区：
文献类型：
--
作者：
Cooles FAH;Anderson AE;Skelton A;Pratt AG;Kurowska-Stolarska MS;McInnes I;Hilkens CMU;Isaacs JD
树突状细胞(DC)是免疫功能的关键协调者。到目前为止，类风湿关节炎(RA)的研究人员主要集中在CD1c+DC的潜在致病作用上。相比之下，CD141+DC和浆细胞样树突状细胞(PDCs)尚未被系统检测，至少在早期RA中是这样。在已建立的RA中，pDC的作用是模糊的，由于病程和治疗都影响RA的病理生理，我们在早期药物未成熟的RA(ERA)患者中检测了pDC和CD1c+和CD141+常规DC(CDCs)。我们分析了ERA患者pDC、CD1c+和CD141+DC的频率和表型，并与健康对照组进行了比较。同时，我们对外周血树突状细胞、CD1c+树突状细胞、B细胞、T细胞和单核细胞的>；600免疫相关基因(纳米串)进行了转录分析。与健康对照组(n = 30)相比，ERA患者(n = 44)所有DC亚群均减少，而对于pDC，这在血清阳性患者中最为明显。CD141+和CD1c+DC，而不是pDC，在基线时具有相对激活的表型(CD86增加)，CD1c+DC频率与疾病活动性呈负相关。所有DC频率在免疫调节治疗开始后12个月保持不变，尽管激活标志物(例如， -DR、CD40)下降。全血干扰素基因特征(IGS)与PDC或CD1c+DC参数无关，但CD141+DC频率与IGS呈负相关。此外，ERA PDC与其他白细胞亚群(B细胞、CD4+、CD8+T细胞和单核细胞)的干扰素-I和干扰素-III的转录产物相似，没有明显的干扰素-I或干扰素-III的循环细胞来源。转录分析显示Era中PDC和CD1c+DC的增殖增加；PDC差异表达的基因也提示耐受功能增强，而CD1c+DC的促炎转录上调。这是第一次详细检查Era外周血中的DC亚群。与CD1c+DC相比，pDC的活性较低，可能偏向于耐受功能。CD141+DC可能参与类风湿关节炎的病理生理过程。我们的发现证明了对早期类风湿关节炎DC生物学的进一步研究。
Dendritic cells (DCs) are key orchestrators of immune function. To date, rheumatoid arthritis (RA) researchers have predominantly focused on a potential pathogenic role for CD1c+ DCs. In contrast, CD141+ DCs and plasmacytoid DCs (pDCs) have not been systematically examined, at least in early RA. In established RA, the role of pDCs is ambiguous and, since disease duration and treatment both impact RA pathophysiology, we examined pDCs, and CD1c+ and CD141+ conventional DCs (cDCs), in early, drug-naïve RA (eRA) patients. We analyzed the frequency and phenotype of pDCs, CD1c+, and CD141+ DCs from eRA patients and compared findings with healthy controls. In parallel, we performed transcriptional analysis of >600 immunology-related genes (Nanostring) from peripheral blood pDCs, CD1c+ DCs, B cells, T cells, and monocytes. All DC subsets were reduced in eRA (n = 44) compared with healthy controls (n = 30) and, for pDCs, this was most marked in seropositive patients. CD141+ and CD1c+ DCs, but not pDCs, had a comparatively activated phenotype at baseline (increased CD86) and CD1c+ DC frequency inversely associated with disease activity. All DC frequencies remained static 12 months after initiation of immunomodulatory therapy despite a fall in activation markers (e.g., HLA-DR, CD40). There was no association between the whole blood interferon gene signature (IGS) and pDC or CD1c+ DC parameters but an inverse association between CD141+ DC frequency and IGS was noted. Furthermore, IFN-I and IFN-III mRNA transcripts were comparable between eRA pDC and other leukocyte subsets (B cells, CD4+, and CD8+ T cells and monocytes) with no obvious circulating cellular source of IFN-I or IFN-III. Transcriptomic analysis suggested increased pDC and CD1c+ DC proliferation in eRA; pDC differentially expressed genes also suggested enhanced tolerogenic function, whereas for CD1c+ DCs, pro-inflammatory transcripts were upregulated. This is the first detailed examination of DC subsets in eRA peripheral blood. Compared with CD1c+ DCs, pDCs are less activated and may be skewed toward tolerogenic functions. CD141+ DCs may be implicated in RA pathophysiology. Our findings justify further investigation of early RA DC biology.
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影响因子：
4.9
作者：
Cavanagh LL;Boyce A;Smith L;Padmanabha J;Filgueira L;Pietschmann P;Thomas R
通讯作者：
Thomas R
影响因子：
13.3
作者：
Chiche, Laurent;Jourde-Chiche, Noemie;Whalen, Elizabeth;Presnell, Scott;Gersuk, Vivian;Dang, Kristen;Anguiano, Esperanza;Quinn, Charlie;Burtey, Stephane;Berland, Yvon;Kaplanski, Gilles;Harle, Jean-Robert;Pascual, Virginia;Chaussabel, Damien
通讯作者：
Chaussabel, Damien
影响因子：
4.4
作者：
Benson, Robert A.;Patakas, Agapitos;Brewer, James M.
通讯作者：
Brewer, James M.
影响因子：
3.7
作者：
Cravens, P. D.;Hayashida, K.;Lipsky, P. E.
通讯作者：
Lipsky, P. E.
影响因子：
15.3
作者：
Dhodapkar, M V;Steinman, R M;Krasovsky, J;Munz, C;Bhardwaj, N
通讯作者：
Bhardwaj, N