AbstractSeveral studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE.

摘要多项研究表明，过敏性鼻炎（AR）是系统性红斑狼疮（SLE）的重要危险因素。然而，缺乏研究AR和SLE之间常见发病机制的研究。我们的研究旨在寻找共享的生物标志物和机制，这些标志物和机制可能为预防AR发展为SLE提供新的治疗靶点。

GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs.

从Gene Expression Omnibus（GEO）数据库下载AR的GSE50223和SLE的GSE103760，以筛选差异表达基因（DEG）。进行了基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）途径富集分析，以探索共享DEG的功能。

Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE.

中枢基因由cytoHubba（Cytoscape的插件）筛选，并在另外两个数据集中进行了验证。应用基因集富集分析（GSEA）和单样本基因集富集分析（ssGSEA）算法来了解中枢基因的功能。ENTPD1被验证为AR和SLE之间的中枢基因。

GSEA results revealed that ENTPD1 was associated with KRAS_SIGNALING_UP pathway in AR and related to HYPOXIA, TGF_BETA_SIGNALING and TNFA_SIGNALING_VIA_NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE..

GSEA结果显示，ENTPD1与AR中的KRAS\u信号通路相关，并通过SLE中的NFKB途径与缺氧，TGF\uβ信号传导和TNFα信号传导有关。在两种疾病中，ENTPD1的表达与活化的CD8 T细胞呈正相关。因此，ENTPD1可能是预防AR发展为SLE的新型治疗靶点。。

IntroductionSystemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by various clinical manifestations ranging from mild skin lesion to disastrous organ damage (e.g., ischemic heart disease, lupus nephritis and pulmonary embolism)1. The prevalence of SLE greatly varies in worldwide regions, such as 84.8, 47, 37.6 and 3299.5 cases per 100,000 persons in San Francisco, France, Chian and Kenya, respectively2,3,4,5.

引言系统性红斑狼疮（SLE）是一种系统性自身免疫性疾病，其特征在于各种临床表现，从轻度皮肤病变到灾难性器官损伤（例如缺血性心脏病，狼疮性肾炎和肺栓塞）1。SLE的患病率在世界各地差异很大，例如旧金山，法国，中国和肯尼亚的每10万人中有84.8,47,37.6和3299.5例，分别为2,3,4,5。

Moreover, SLE is the leading death reason among young women6. Thus, early detection, early diagnosis and effective treatment of SLE are warranted. Currently, the clinical treatments for SLE include corticosteroids, immunomodulators, cytotoxic-immunosuppressants, and biologics such as rituximab7. Nevertheless, there are some limitations to current therapies.

此外，SLE是年轻女性的主要死亡原因6。因此，有必要对SLE进行早期发现，早期诊断和有效治疗。目前，SLE的临床治疗包括皮质类固醇，免疫调节剂，细胞毒性免疫抑制剂和生物制剂，如利妥昔单抗7。然而，目前的疗法存在一些局限性。

For example, the consumption of B cells induced by rituximab may result in the absence of persistent response to rituximab. Thus, further investigations into new therapeutic strategies are necessitated.Allergic rhinitis (AR) is a chronic nasal disorder mainly mediated by immunoglobulin E (IgE), whose mechanism involves various kinds of immune cells8.

例如，利妥昔单抗诱导的B细胞消耗可能导致对利妥昔单抗没有持续反应。因此，有必要进一步研究新的治疗策略。过敏性鼻炎（AR）是一种主要由免疫球蛋白E（IgE）介导的慢性鼻腔疾病，其机制涉及多种免疫细胞8。

The symptoms of AR including nasal itching, nasal obstruction, sneezing and rhinorrhea have bothered 10–40% of the population globally9. Superficially, AR and SLE seem to be no correlation, but accumulated pieces of research studies suggest that AR is a significant risk factor of SLE10,11,12,13. A meta-analysis study reviewed 1 cohort and 7 case–control studies, and indicated that individuals with AR had a 1.36-fold risk of SLE compared with individuals without AR13.

AR的症状包括鼻痒，鼻塞，打喷嚏和鼻漏，困扰着全球10-40%的人口9。从表面上看，AR和SLE似乎没有相关性，但累积的研究表明AR是SLE10,11,12,13的重要危险因素。一项荟萃分析研究回顾了1项队列研究和7项病例对照研究，结果表明，与没有AR13的个体相比，患有AR的个体患SLE的风险是其1.36倍。

These intriguing findings inspired us to investigate the potential common mechanisms between AR and SLE in search of novel biological targets.CD4+T cells are mainly .

这些有趣的发现启发我们研究AR和SLE之间潜在的共同机制，以寻找新的生物靶标。CD4+T细胞主要是。

To uncover the effect of ENTPD1 on AR and SLE, GSEA was utilized to explore the significantly different pathways involved in these two diseases between the low and high ENTPD1 expression groups. GSEA result reveals that ENTPD1 is significantly associated with KRAS_SIGNALING_UP pathway in AR (Fig. S3a).

为了揭示ENTPD1对AR和SLE的影响，利用GSEA探索了低和高ENTPD1表达组之间这两种疾病的显着不同途径。GSEA结果显示ENTPD1与AR中的KRAS\u信号通路显着相关（图S3a）。

In addition, ENTPD1 is strongly related to HYPOXIA, TGF_BETA_SIGNALING, and TNFA_SIGNALING_VIA_NFKB pathways in SLE (Fig. S3b). The P-values, ES, NES and FDR for GSE50223 and GSE103760 were listed in Table S6.Immune infiltration analyses of ENTPD1.

此外，ENTPD1通过SLE中的NFKB途径与缺氧，TGF\uβ信号传导和TNFA\u信号传导密切相关（图S3b）。表S6列出了GSE50223和GSE103760的P值，ES，NES和FDR。ENTPD1的免疫浸润分析。

We obtained the associations between the expression of ENTPD1 and immune cell infiltration in AR and SLE via the ssGSEA algorithm and spearman’s correlation analysis. The Fig. S4 shows the activated CD4 T cell and effector memory CD4 T cell are more highly expressed in AR and SLE patients compared with controls.

我们通过ssGSEA算法和spearman相关分析获得了AR和SLE中ENTPD1表达与免疫细胞浸润之间的关联。图S4显示，与对照组相比，AR和SLE患者中活化的CD4 T细胞和效应记忆CD4 T细胞表达更高。

As revealed by Fig. 7a, the expression of ENTPD1 is positively related to activated CD8 T cell and eosinophil, and is negatively linked with regulatory T cell, macrophage, gamma delta T cell and activated dendritic cell in AR. Moreover, immune infiltration analysis was also performed in SLE, which indicated that ENTPD1 expression was positively associated with type 2 T helper cell, gamma delta T cell, memory B cell, regulatory T cell, activated CD4 T cell, effector memory CD8 T cell, plasmacytoid dendritic cell, activated CD8 T cell, and activated B cell (Fig. 7b).

如图7a所示，ENTPD1的表达与活化的CD8 T细胞和嗜酸性粒细胞呈正相关，与AR中的调节性T细胞，巨噬细胞，γδT细胞和活化的树突状细胞呈负相关。此外，免疫浸润分析也在SLE中进行，这表明ENTPD1表达与2型T辅助细胞，γδT细胞，记忆B细胞，调节性T细胞，活化的CD4 T细胞，效应记忆CD8 T细胞，浆细胞样树突状细胞，活化的CD8 T细胞和活化的B细胞呈正相关（图7b）。

Clearly, the expression of ENTPD1 was positively correlated with activated CD8 T cell in both AR and SLE.Figure 7Distribution of immune cell infiltration in AR and SLE. The lollipop plots reveal the relationships between ENTPD1 expression level and immune cell subtypes in AR (a) and SLE patients (b).

显然，在AR和SLE中，ENTPD1的表达与活化的CD8 T细胞呈正相关。图7 AR和SLE中免疫细胞浸润的分布。棒棒糖图揭示了AR（a）和SLE患者（b）中ENTPD1表达水平与免疫细胞亚型之间的关系。

AR allergic rhinitis, SLE systemic lupus erythematosus.Full size imageCandidate chemical compounds targeting at ENTPD1 in the CTDSince ENTPD1 might play a key role in the pathogenesis of AR and SLE, we next investigated to search for the potential compounds that regulated the expression of ENTPD1. Table S7 describes candidate chemical compounds which could regulate ENTPD1 mRNA expression.

AR过敏性鼻炎，SLE系统性红斑狼疮。全尺寸图像CTD中靶向ENTPD1的候选化合物由于ENTPD1可能在AR和SLE的发病机制中起关键作用，我们接下来研究寻找调节ENTPD1表达的潜在化合物。表S7描述了可以调节ENTPD1 mRNA表达的候选化合物。

There were 10 chemical compounds decreasing ENTPD1 expression and 13 chemical compounds increasing ENTPD1 expression.DiscussionSLE usually causes catastrophic organ damage and is the primary reason of young female6. Howe.

有10种化合物降低了ENTPD1的表达，有13种化合物增加了ENTPD1的表达。讨论通常会导致灾难性的器官损伤，是年轻女性的主要原因6。豪。

Data availability

数据可用性

The datasets analyzed during the current study are available in the GEO repository at www.ncbi.nlm.nih.gov/geo/ (accession number: GSE103760, GSE50223, GSE44960 and GSE10325).

当前研究期间分析的数据集可在GEO存储库中获得，网址为www.ncbi.nlm.nih.gov/GEO/（登录号：GSE103760，GSE50223，GSE44960和GSE10325）。

ReferencesBarber, M. R. W. et al. Global epidemiology of systemic lupus erythematosus. Nat. Rev. Rheumatol. 17, 515–532 (2021).Article

参考文献Barber，M.R.W.等人，《系统性红斑狼疮的全球流行病学》。风湿病杂志。17515-532（2021）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Dall’Era, M. et al. The incidence and prevalence of systemic lupus erythematosus in San Francisco County, California: The california lupus surveillance project. Arthritis Rheumatol. 69, 1996–2005 (2017).Article

Dall'Era，M.等人。加利福尼亚州旧金山县系统性红斑狼疮的发病率和患病率：加利福尼亚狼疮监测项目。风湿性关节炎。691996-2005（2017）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Arnaud, L. et al. Prevalence and incidence of systemic lupus erythematosus in France: A 2010 nation-wide population-based study. Autoimmun. Rev. 13, 1082–1089 (2014).Article

Arnaud，L.等人，《法国系统性红斑狼疮的患病率和发病率：2010年全国人群研究》。自身免疫。第13版，1082–1089（2014）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Ekwom, P. E. Systemic lupus erythematosus (SLE) at the Kenyatta National Hospital. Clin. Rheumatol. 32, 1215–1217 (2013).Article

Ekwom，P.E。肯雅塔国立医院的系统性红斑狼疮（SLE）。临床。风湿病。321215-1217（2013）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Zou, Y. F. et al. Prevalence of systemic lupus erythematosus and risk factors in rural areas of Anhui Province. Rheumatol. Int. 34, 347–356 (2014).Article

邹永福等。安徽省农村地区系统性红斑狼疮患病率及危险因素分析。风湿病。Int.34347–356（2014年）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Yen, E. Y. & Singh, R. R. Brief report: Lupus-an Unrecognized leading cause of death in young females: A population-based study using nationwide death certificates, 2000–2015. Arthritis Rheumatol. 70, 1251–1255 (2018).Article

Yen，E.Y.＆Singh，R.R.简要报告：狼疮是年轻女性未被认识的主要死亡原因：一项使用全国死亡证明的基于人群的研究，2000-2015年。风湿性关节炎。701251-1255（2018）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fava, A. & Petri, M. Systemic lupus erythematosus: Diagnosis and clinical management. J. Autoimmun. 96, 1–13 (2019).Article

Fava，A。＆Petri，M。系统性红斑狼疮：诊断和临床管理。J、 自身免疫。。文章

PubMed

PubMed

Google Scholar

谷歌学者

Bousquet, J. et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 63(Suppl 86), 8–160 (2008).Article

Bousquet，J.等人，《过敏性鼻炎及其对哮喘的影响》（ARIA）2008年更新（与世界卫生组织合作，GA（2）LEN和过敏原）。。文章

PubMed

PubMed

Google Scholar

谷歌学者

Hong, H., Liao, S., Chen, F., Yang, Q. & Wang, D. Y. Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation. Allergy 75, 2794–2804 (2020).Article

Hong，H.，Liao，S.，Chen，F.，Yang，Q。＆Wang，D.Y。IL-25，IL-33和TSLP在引发联合气道疾病向2型炎症中的作用。过敏752794-2804（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hsiao, Y. P. et al. Atopic diseases and systemic lupus erythematosus: An epidemiological study of the risks and correlations. Int. J. Environ. Res. Public Health 11, 8112–8122 (2014).Article

Hsiao，Y.P.等。特应性疾病和系统性红斑狼疮：风险和相关性的流行病学研究。内景J.环境。Res.Public Health 118112–8122（2014）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hou, Y. C., Hu, H. Y., Liu, I. L., Chang, Y. T. & Wu, C. Y. The risk of autoimmune connective tissue diseases in patients with atopy: A nationwide population-based cohort study. Allergy Asthma Proc. 38, 383–389 (2017).Article

Hou，Y.C.，Hu，H.Y.，Liu，I.L.，Chang，Y.T.＆Wu，C.Y.特应性患者自身免疫性结缔组织病的风险：一项全国范围的基于人群的队列研究。过敏性哮喘程序。38383-389（2017）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Krishna, M. T. et al. Allergic diseases and long-term risk of autoimmune disorders: Longitudinal cohort study and cluster analysis. Eur. Respir J. 54(5), 1900476 (2019).Article

Krishna，M.T.等人，《过敏性疾病和自身免疫性疾病的长期风险：纵向队列研究和聚类分析》。《欧洲呼吸杂志》54（5），1900476（2019）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Wongtrakul, W., Charoenngam, N., Ponvilawan, B. & Ungprasert, P. Allergic rhinitis and risk of systemic lupus erythematosus: A systematic review and meta-analysis. Int. J. Rheum. Dis. 23, 1460–1467 (2020).Article

Wongtrakul，W.，Charoenngam，N.，Ponvilawan，B。＆Ungprasert，P。过敏性鼻炎和系统性红斑狼疮的风险：系统评价和荟萃分析。内景J.Rheum。。231460-1467（2020）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Ruterbusch, M., Pruner, K. B., Shehata, L. & Pepper, M. In Vivo CD4(+) T Cell differentiation and function: Revisiting the Th1/Th2 paradigm. Annu. Rev. Immunol. 38, 705–725 (2020).Article

Ruterbusch，M.，Pruner，K.B.，Shehata，L。和Pepper，M。体内CD4（+）T细胞分化和功能：重新审视Th1/Th2范式。年。免疫修订版。38705-725（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Pan, L., Lu, M. P., Wang, J. H., Xu, M. & Yang, S. R. Immunological pathogenesis and treatment of systemic lupus erythematosus. World J. Pediatr. 16, 19–30 (2020).Article

Pan，L.，Lu，M.P.，Wang，J.H.，Xu，M。和Yang，S.R。系统性红斑狼疮的免疫发病机制和治疗。世界J.儿科。16，19-30（2020）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Gupta, R. K., Gupta, K. & Dwivedi, P. D. Pathophysiology of IL-33 and IL-17 in allergic disorders. Cytokine Growth Factor Rev. 38, 22–36 (2017).Article

Gupta，R.K.，Gupta，K。＆Dwivedi，P.D。IL-33和IL-17在过敏性疾病中的病理生理学。细胞因子生长因子Rev.38,22-36（2017）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zhang, Y., Lan, F. & Zhang, L. Update on pathomechanisms and treatments in allergic rhinitis. Allergy 77, 3309–3319 (2022).Article

Zhang，Y.，Lan，F。＆Zhang，L。过敏性鼻炎发病机制和治疗的最新进展。过敏773309-3319（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yan, Z. et al. Bioinformatics analysis and identification of underlying biomarkers potentially linking allergic rhinitis and asthma. Med. Sci. Monit. 26, e924934 (2020).Article

Yan，Z.等人。生物信息学分析和鉴定可能与过敏性鼻炎和哮喘相关的潜在生物标志物。医学科学。莫尼特。26，e924934（2020）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yao, M. et al. Exploration of the shared gene signatures and molecular mechanisms between systemic lupus erythematosus and pulmonary arterial hypertension: Evidence from transcriptome data. Front. Immunol. 12, 658341 (2021).Article

Yao，M.等人。探索系统性红斑狼疮和肺动脉高压之间共享的基因特征和分子机制：来自转录组数据的证据。正面。免疫。12658341（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucl. Acids Res. 28, 27–30 (2000).Article

Kanehisa，M。＆Goto，S。KEGG：京都基因与基因组百科全书。核。《酸决议》28，27–30（2000）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucl. Acids Res. 51, D587–D592 (2023).Article

Kanehisa，M.，Furumichi，M.，Sato，Y.，Kawashima，M。＆Ishiguro Watanabe，M。KEGG用于基于分类学的途径和基因组分析。核。Acids Res.51，D587–D592（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947–1951 (2019).Article

Kanehisa，M。了解细胞生物的起源和进化。蛋白质科学。281947-1951（2019）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chin, C. H. et al. cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol. 8(Suppl 4), S11 (2014).Article

Chin，C.H.等人。cytoHubba：从复杂的相互作用组中识别中枢对象和子网络。。生物学8（补充4），S11（2014）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Davis, A. P. et al. The Comparative Toxicogenomics database: Update 2017. Nucl. Acids Res. 45, D972–D978 (2017).Article

Davis，A.P.等人，《比较毒理基因组学数据库：2017年更新》。核。Acids Res.45，D972–D978（2017）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Aringer, M. et al. 2019 European league against rheumatism/American college of rheumatology classification criteria for systemic lupus erythematosus. Ann. Rheum. Dis. 78, 1151–1159 (2019).Article

Aringer，M.等人，2019年欧洲风湿病联盟/美国风湿病学会系统性红斑狼疮分类标准。安。瑞姆。。781151-1159（2019）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Warde-Farley, D. et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucl. Acids Res. 38, W214–W220 (2010).Article

Warde Farley，D。等人，《GeneMANIA预测服务器：用于基因优先排序和预测基因功能的生物网络集成》。核。Acids Res.38，W214–W220（2010）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Finotello, F. & Trajanoski, Z. Quantifying tumor-infiltrating immune cells from transcriptomics data. Cancer Immunol. Immunother. 67, 1031–1040 (2018).Article

。癌症免疫。免疫疗法。671031-1040（2018）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ocampo-Piraquive, V., Nieto-Aristizábal, I., Cañas, C. A. & Tobón, G. J. Mortality in systemic lupus erythematosus: Causes, predictors and interventions. Exp. Rev. Clin. Immunol. 14, 1043–1053 (2018).Article

Ocampo Piraquive，V.，Nieto Aristizábal，I.，Cañas，C.A。＆Tobón，G.J。系统性红斑狼疮的死亡率：原因，预测因素和干预措施。实验修订临床。免疫。141043-1053（2018）。文章

CAS

中科院

Google Scholar

谷歌学者

Kirtland, M. E., Tsitoura, D. C., Durham, S. R. & Shamji, M. H. Toll-Like receptor agonists as adjuvants for allergen immunotherapy. Front. Immunol. 11, 599083 (2020).Article

Kirtland，M.E.，Tsitoura，D.C.，Durham，S.R。＆Shamji，M.H。Toll样受体激动剂作为过敏原免疫治疗的佐剂。正面。免疫。11599083（2020）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fillatreau, S., Manfroi, B. & Dörner, T. Toll-like receptor signalling in B cells during systemic lupus erythematosus. Nat. Rev. Rheumatol. 17, 98–108 (2021).Article

Fillatreau，S.，Manfroi，B。＆Dörner，T。系统性红斑狼疮期间B细胞中的Toll样受体信号传导。风湿病杂志。17，98-108（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Timperi, E. & Barnaba, V. CD39 Regulation and Functions in T Cells. Int. J. Mol. Sci. 22(15), 8068 (2021).Article

Timperi，E。＆Barnaba，V。CD39在T细胞中的调节和功能。Int.J.Mol.Sci。22（15），8068（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Becker, L. V., Passos, D. F., Leal, D. B. R., Morsch, V. M. & Schetinger, M. R. C. ATP signaling and NTPDase in systemic lupus erythematosus (SLE). Immunobiology 224, 419–426 (2019).Article

Becker，L.V.，Passos，D.F.，Leal，D.B.R.，Morsch，V.M。＆Schetinger，M.R.C。系统性红斑狼疮（SLE）中的ATP信号传导和NTPDase。免疫生物学224419-426（2019）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Becker, L. V. et al. Activity and expression of E-NTPDase is altered in peripheral lymphocytes of systemic lupus erythematosus patients. Clin. Chim. acta Int. J. Clin. Chem. 488, 90–7 (2019).Article

Becker，L.V.等人。系统性红斑狼疮患者外周血淋巴细胞中E-NTPDase的活性和表达发生改变。临床。奇姆。。化学。488,90-7（2019）。文章

CAS

中科院

Google Scholar

谷歌学者

Loza, M. J., Anderson, A. S., O’Rourke, K. S., Wood, J. & Khan, I. U. T-cell specific defect in expression of the NTPDase CD39 as a biomarker for lupus. Cell Immunol. 271, 110–117 (2011).Article

Loza，M.J.，Anderson，A.S.，O'Rourke，K.S.，Wood，J。＆Khan，I.U。NTPDase CD39作为狼疮生物标志物表达的T细胞特异性缺陷。细胞免疫。271110-117（2011）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Knight, J. S. et al. Ectonucleotidase-mediated suppression of lupus autoimmunity and vascular dysfunction. Front. Immunol. 9, 1322 (2018).Article

Knight，J.S.等人。外核苷酸酶介导的狼疮自身免疫和血管功能障碍的抑制。正面。免疫。91322（2018）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Dang, J. et al. Human gingiva-derived mesenchymal stem cells are therapeutic in lupus nephritis through targeting of CD39(-)CD73 signaling pathway. J. Autoimmun. 113, 102491 (2020).Article

Dang，J。等人。人牙龈间充质干细胞通过靶向CD39（-）CD73信号通路治疗狼疮性肾炎。J、 自身免疫。113102491（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zhang, X. et al. CD8+CD103+ iTregs inhibit chronic graft-versus-host disease with lupus nephritis by the increased expression of CD39. Mol. Ther J. Am. Soc. Gene Ther. 27, 1963–1973 (2019).Article

Zhang，X。等。CD8+CD103+iTregs通过增加CD39的表达来抑制狼疮性肾炎的慢性移植物抗宿主病。。271963-1973（2019）。文章

ADS

广告

CAS

中科院

Google Scholar

谷歌学者

Melchiotti, R. et al. Genetic analysis of an allergic rhinitis cohort reveals an intercellular epistasis between FAM134B and CD39. BMC Med. Genet. 15, 73 (2014).Article

Melchiotti，R。等人。过敏性鼻炎队列的遗传分析揭示了FAM134B和CD39之间的细胞间上位性。BMC医学基因。15，73（2014）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Moitra, S. et al. Modulation of regulatory T cells by intranasal allergen immunotherapy in an experimental rat model of airway allergy. Int. Immunopharmacol. 47, 9–19 (2017).Article

Moitra，S.等人。气道过敏实验大鼠模型中鼻内过敏原免疫疗法对调节性T细胞的调节。国际免疫药理学。47,9-19（2017）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Montuori-Andrade, A. C. M. et al. Lactobacillus delbrueckii UFV-H2b20 increases IFN-gamma production and CD39(+)CD73(+) Treg cell numbers in lungs, and protects mice against experimental allergic asthma. Immunobiology 227, 152284 (2022).Article

Montuori Andrade，A.C.M.等人，德氏乳杆菌UFV-H2b20增加肺中IFN-γ产生和CD39（+）CD73（+）Treg细胞数量，并保护小鼠免受实验性过敏性哮喘的影响。免疫生物学227152284（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Huang, Y. A. et al. Reducing lung ATP levels and alleviating asthmatic airway inflammation through adeno-associated viral vector-mediated CD39 expression. Biomedicines 9(6), 656 (2021).Article

Huang，Y.A.等人。通过腺相关病毒载体介导的CD39表达降低肺ATP水平并减轻哮喘气道炎症。生物医学9（6），656（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Li, P. et al. CD39+ regulatory T cells attenuate allergic airway inflammation. Clin. Exp. Allergy 45, 1126–1137 (2015).Article

。临床。实验过敏451126-1137（2015）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Li, P., Cao, J., Chen, Y., Wang, W. & Yang, J. Apyrase protects against allergic airway inflammation by decreasing the chemotactic migration of dendritic cells in mice. Int. J. Mol. Med. 34, 269–275 (2014).Article

Li，P.，Cao，J.，Chen，Y.，Wang，W。＆Yang，J。Apyrase通过减少小鼠树突状细胞的趋化性迁移来预防过敏性气道炎症。《国际分子医学杂志》34269-275（2014）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Lu, Y., Li, Y., Zhou, W., Ding, B. & Yu, Q. Regulatory T cells regulate the distribution of natural killer T cells through CD39 signal transduction in asthma. Hum. Cell 32, 141–149 (2019).Article

Lu，Y.，Li，Y.，Zhou，W.，Ding，B。＆Yu，Q。调节性T细胞通过CD39信号转导调节哮喘中自然杀伤T细胞的分布。嗯，《细胞》32141-149（2019）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Wing, J. B., Tanaka, A. & Sakaguchi, S. Human FOXP3(+) regulatory T cell heterogeneity and function in autoimmunity and cancer. Immunity 50, 302–316 (2019).Article

Wing，J.B.，Tanaka，A。＆Sakaguchi，S。人类FOXP3（+）调节性T细胞异质性和自身免疫和癌症中的功能。豁免50302-316（2019）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Paiva Ferreira, L. K. D. et al. Combined allergic rhinitis and asthma syndrome (CARAS). Int. Immunopharmacol. 74, 105718 (2019).Article

Paiva Ferreira，L.K.D.等人联合过敏性鼻炎和哮喘综合征（CARAS）。国际免疫药理学。74105718（2019）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Suzuki, M. et al. IFN-gamma secretion by CD8T cells inhibits allergen-induced airway eosinophilia but not late airway responses. J. Allergy Clin. Immunol. 109, 803–809 (2002).Article

Suzuki，M。等人。CD8T细胞分泌IFN-γ抑制过敏原诱导的气道嗜酸性粒细胞增多，但不抑制晚期气道反应。J、 过敏临床。免疫。109803-809（2002）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Lin, L., Dai, F., Wei, J. & Chen, Z. Influences of CD8(+) Tregs on peripheral blood mononuclear cells from allergic rhinitis patients. The Laryngoscope 131, E316–E323 (2021).Article

Lin，L.，Dai，F.，Wei，J。＆Chen，Z。CD8（+）Tregs对过敏性鼻炎患者外周血单核细胞的影响。喉镜131，E316–E323（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Li, J. et al. KIR(+)CD8(+) T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19. Science (New York, NY). 376, eabi9591 (2022).Article

Li，J。等人。KIR（+）CD8（+）T细胞抑制致病性T细胞，并在自身免疫性疾病和COVID-19中具有活性。科学（纽约，纽约）。376，eabi9591（2022）。文章

CAS

中科院

Google Scholar

谷歌学者

Saligrama, N. et al. Opposing T cell responses in experimental autoimmune encephalomyelitis. Nature 572, 481–487 (2019).Article

。自然572481-487（2019）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Krasselt, M. & Baerwald, C. Sex, symptom severity, and quality of life in rheumatology. Clin. Rev. Allergy Immunol. 56, 346–361 (2019).Article

Krasselt，M。＆Baerwald，C。风湿病的性别，症状严重程度和生活质量。临床。版本过敏免疫。56346-361（2019）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Drosten, M. & Barbacid, M. Targeting the MAPK pathway in KRAS-driven tumors. Cancer cell. 37, 543–550 (2020).Article

。癌细胞。37543-550（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Aringer, M. Inflammatory markers in systemic lupus erythematosus. J. Autoimmun. 110, 102374 (2020).Article

Aringer，M。系统性红斑狼疮中的炎症标志物。J、 自身免疫。110102374（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liu, Y. et al. The TGF-β/miR-31/CEACAM1-S axis inhibits CD4(+) CD25(+) Treg differentiation in systemic lupus erythematosus. Immunol. Cell Biol. 99, 697–710 (2021).Article

Liu，Y。等人。TGF-β/miR-31/CEACAM1-S轴抑制系统性红斑狼疮中的CD4（+）CD25（+）Treg分化。免疫。细胞生物学。99697-710（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Alexander, T. & Hedrich, C. M. Systemic lupus erythematosus—Are children miniature adults?. Clin. Immunol. 234, 108907 (2022).Article

Alexander，T。＆Hedrich，C.M。系统性红斑狼疮是儿童微型成人吗？。临床。免疫。234108907（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Niu, H. Q. et al. Characteristics and reference ranges of CD4(+)T cell subpopulations among healthy adult Han Chinese in Shanxi Province, North China. BMC Immunol. 21, 44 (2020).Article

Niu，H.Q.等人。中国北方山西省健康成年汉族人CD4（+）T细胞亚群的特征和参考范围。BMC免疫。21，44（2020）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesAcknowledgementsThe authors gratefully acknowledged the financial supports by the National Natural Science Foundation of China under Grant numbers 81200734.FundingThis study was supported by a grant (No.81200734) from the National Natural Science Foundation of China.Author informationAuthor notesThese authors contributed equally: Min Chen and Yingdi Meng.Authors and AffiliationsDepartment of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai, 200433, ChinaMin Chen, Yingdi Meng, Xiaoqiong Shi, Chengjing Zhu, Minhui Zhu, Haihong Tang & Hongliang ZhengAuthorsMin ChenView author publicationsYou can also search for this author in.

下载参考文献致谢作者非常感谢国家自然科学基金会在资助号81200734下提供的财政支持。资助本研究得到了国家自然科学基金会（No.81200734）的资助。作者信息作者注意到这些作者做出了同样的贡献：陈敏和孟英迪。作者和附属机构海军医科大学第一附属医院耳鼻咽喉头颈外科，上海市杨浦区长海路168号，200433，中国陈敏，孟英迪，石晓琼，朱程静，朱敏辉，唐海红和郑洪亮作者陈敏观点作者出版物你也可以在中搜索这位作者。

PubMed Google ScholarYingdi MengView author publicationsYou can also search for this author in

PubMed Google ScholarYingdi MengView作者出版物您也可以在

PubMed Google ScholarXiaoqiong ShiView author publicationsYou can also search for this author in

PubMed Google ScholarXiaoqiong ShiView作者出版物您也可以在

PubMed Google ScholarChengjing ZhuView author publicationsYou can also search for this author in

PubMed Google ScholarChengjing ZhuView作者出版物您也可以在

PubMed Google ScholarMinhui ZhuView author publicationsYou can also search for this author in

PubMed Google Scholarmaminhui ZhuView作者出版物您也可以在

PubMed Google ScholarHaihong TangView author publicationsYou can also search for this author in

PubMed谷歌学者Haihong TangView作者出版物您也可以在

PubMed Google ScholarHongliang ZhengView author publicationsYou can also search for this author in

PubMed谷歌学者郑洪亮查看作者出版物您也可以在

PubMed Google ScholarContributionsH.Z., H.T. and M.Z. contributed to the study conception and design. Data analysis was performed by M.C. and C.Z. The first draft of the manuscript was written by M.C., X.S. and Y.M. And all authors commented on previous versions of the manuscript.

PubMed谷歌学术贡献。Z、 ，H.T.和M.Z.为研究概念和设计做出了贡献。数据分析由M.C.和C.Z.进行。手稿的初稿由M.C.，X.S.和Y.M.撰写，所有作者都对手稿的以前版本发表了评论。

All authors read and approved the final manuscript.Corresponding authorsCorrespondence to.

所有作者都阅读并批准了最终稿件。通讯作者通讯。

Minhui Zhu, Haihong Tang or Hongliang Zheng.Ethics declarations

。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Additional informationPublisher's noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary InformationSupplementary Information.Rights and permissions

Additional informationPublisher的noteSpringer Nature在已发布地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充信息。权限和权限

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

开放获取本文是根据知识共享署名非商业性NoDerivatives 4.0国际许可证授权的，该许可证允许以任何媒介或格式进行任何非商业性使用，共享，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出您是否修改了许可材料。

You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

根据本许可证，您无权共享源自本文或其部分的改编材料。本文中的图像或其他第三方材料包含在文章的知识共享许可证中，除非该材料的信用额度中另有说明。。

To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by-nc-nd/4.0/..

Reprints and permissionsAbout this articleCite this articleChen, M., Meng, Y., Shi, X. et al. Identification of ENTPD1 as a novel biomarker linking allergic rhinitis and systemic lupus erythematosus.

。

Sci Rep 14, 18266 (2024). https://doi.org/10.1038/s41598-024-69228-3Download citationReceived: 22 February 2024Accepted: 01 August 2024Published: 06 August 2024DOI: https://doi.org/10.1038/s41598-024-69228-3Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1418266（2024）。https://doi.org/10.1038/s41598-024-69228-3Download引文接收日期：2024年2月22日接受日期：2024年8月1日发布日期：2024年8月6日OI：https://doi.org/10.1038/s41598-024-69228-3Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

Keywords

关键词

ENTPD1

ENTPD1

CD4+T cellsAllergic rhinitisSystemic lupus erythematosusBioinformatics

CD4+T细胞过敏性鼻炎系统性红斑狼疮生物信息学

CommentsBy submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

评论通过提交评论，您同意遵守我们的条款和社区指南。如果您发现有虐待行为或不符合我们的条款或准则，请将其标记为不合适。