microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome
Abstract Objective To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFNα in SLE and APS, and miRNAs are emerging as regulators of pDC activation. Methods miRNA and mRNA expression were measured by...
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| Veröffentlicht in: | Rheumatology (Oxford, England) England), 2018-09, Vol.57 (9), p.1669-1674 |
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| creator | van den Hoogen, Lucas L Rossato, Marzia Lopes, Ana P Pandit, Aridaman Bekker, Cornelis P J Fritsch-Stork, Ruth D E van Roon, Joel A G Radstake, Timothy R D J |
| description | Abstract
Objective
To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFNα in SLE and APS, and miRNAs are emerging as regulators of pDC activation.
Methods
miRNA and mRNA expression were measured by OpenArray and RNA-sequencing in pDCs of SLE, SLE + APS (APS secondary to SLE) and primary APS (PAPS) patients. The miRNA profile of patients was compared with the miRNA pattern of TLR7-activated pDCs.
Results
Among 131 miRNAs detected in pDCs, 35, 17 and 21 had a significantly lower level of expression in SLE, SLE + APS and PAPS patients, respectively, as compared with healthy controls (HC). Notably, the miRNA profile did not significantly differ between SLE and APS, but was driven by the presence or absence of an IFN signature. TLR7 stimulation induced a general downregulation of miRNAs, similar to the pattern observed in SLE and APS patients. miR-361-5p, miR-128-3p and miR-181a-2-3p expression was lower in patients with a high IFN signature (false discovery rate |
| doi_str_mv | 10.1093/rheumatology/key159 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2051064800</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/rheumatology/key159</oup_id><sourcerecordid>2306549523</sourcerecordid><originalsourceid>FETCH-LOGICAL-c483t-d6d399233e5a325d669433356197bebea3d19a265a1d533de769f6edcc6553f3</originalsourceid><addsrcrecordid>eNqNkd1KJDEQhcOiqDv6BAtLgzfetCapTmZyKeL-gOyCeN9kOtVO3O6kzY_Sj7BvbYZRWbzaiyIJderjpA4hXxg9Z1TBRdhgHnXyg7-fL_7gzIT6RI5YI3lNAfje-503h-RzjA-UUsFgdUAOuVotYSnlEfk72i7421-XlfHPLuB9HnSy3lXWVdOg46i7OXlrKoPOBJtsV3U4DHHbty5h6DF4V08-lt4TVnGOCQuzGvKUY4VhThvcuozlpZ0pley08bHUYKcCjnMB-xGPyX6vh4gnr-eC3H27vrv6Ud_8_v7z6vKm7poVpNpIA0pxABQauDBSqgYAhGRqucY1ajBMaS6FZkYAGFxK1Us0XSeFgB4W5GyHnYJ_zBhTO9q4_ZJ26HNsedkRlc2K0iI9_SB98Dm4Yq7lQKVolCg-FgR2qrLHGAP27RTsqMPcMtpug2r_DardBVWmvr6y83pE8z7zlkwRnO8EPk__RXwBlJOogA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2306549523</pqid></control><display><type>article</type><title>microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>van den Hoogen, Lucas L ; Rossato, Marzia ; Lopes, Ana P ; Pandit, Aridaman ; Bekker, Cornelis P J ; Fritsch-Stork, Ruth D E ; van Roon, Joel A G ; Radstake, Timothy R D J</creator><creatorcontrib>van den Hoogen, Lucas L ; Rossato, Marzia ; Lopes, Ana P ; Pandit, Aridaman ; Bekker, Cornelis P J ; Fritsch-Stork, Ruth D E ; van Roon, Joel A G ; Radstake, Timothy R D J</creatorcontrib><description>Abstract
Objective
To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFNα in SLE and APS, and miRNAs are emerging as regulators of pDC activation.
Methods
miRNA and mRNA expression were measured by OpenArray and RNA-sequencing in pDCs of SLE, SLE + APS (APS secondary to SLE) and primary APS (PAPS) patients. The miRNA profile of patients was compared with the miRNA pattern of TLR7-activated pDCs.
Results
Among 131 miRNAs detected in pDCs, 35, 17 and 21 had a significantly lower level of expression in SLE, SLE + APS and PAPS patients, respectively, as compared with healthy controls (HC). Notably, the miRNA profile did not significantly differ between SLE and APS, but was driven by the presence or absence of an IFN signature. TLR7 stimulation induced a general downregulation of miRNAs, similar to the pattern observed in SLE and APS patients. miR-361-5p, miR-128-3p and miR-181a-2-3p expression was lower in patients with a high IFN signature (false discovery rate <0.05) as compared with patients with a low IFN signature and HCs. Pathway enrichment on the overlap of miRNA targets and upregulated genes from the RNAseq indicated that these miRNAs are involved in pDC activation and apoptosis.
Conclusion
Lower miRNA expression in pDCs is shared between SLE, SLE + APS and PAPS and is related to the IFN signature. As pDCs are the alleged source of the IFN signature in these patients, a better understanding of the molecular mechanisms/pathways leading to pDC dysregulation in SLE and APS might open novel pathways for therapeutic intervention.</description><identifier>ISSN: 1462-0324</identifier><identifier>EISSN: 1462-0332</identifier><identifier>DOI: 10.1093/rheumatology/key159</identifier><identifier>PMID: 29873766</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult ; Antiphospholipid syndrome ; Antiphospholipid Syndrome - genetics ; Antiphospholipid Syndrome - metabolism ; Apoptosis ; Autoimmune diseases ; Dendritic cells ; Dendritic Cells - metabolism ; Dendritic Cells - pathology ; Down-Regulation ; Female ; Gene expression ; Gene Expression Regulation ; Humans ; Interferon ; Lupus ; Lupus Erythematosus, Systemic - genetics ; Lupus Erythematosus, Systemic - metabolism ; Lupus Erythematosus, Systemic - pathology ; Male ; MicroRNAs ; MicroRNAs - biosynthesis ; MicroRNAs - genetics ; miRNA ; Molecular modelling ; RNA, Messenger - genetics ; Systemic lupus erythematosus ; TLR7 protein ; Toll-Like Receptor 7 - biosynthesis ; Toll-Like Receptor 7 - genetics ; Toll-like receptors ; α-Interferon</subject><ispartof>Rheumatology (Oxford, England), 2018-09, Vol.57 (9), p.1669-1674</ispartof><rights>The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com 2018</rights><rights>The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-d6d399233e5a325d669433356197bebea3d19a265a1d533de769f6edcc6553f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29873766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van den Hoogen, Lucas L</creatorcontrib><creatorcontrib>Rossato, Marzia</creatorcontrib><creatorcontrib>Lopes, Ana P</creatorcontrib><creatorcontrib>Pandit, Aridaman</creatorcontrib><creatorcontrib>Bekker, Cornelis P J</creatorcontrib><creatorcontrib>Fritsch-Stork, Ruth D E</creatorcontrib><creatorcontrib>van Roon, Joel A G</creatorcontrib><creatorcontrib>Radstake, Timothy R D J</creatorcontrib><title>microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome</title><title>Rheumatology (Oxford, England)</title><addtitle>Rheumatology (Oxford)</addtitle><description>Abstract
Objective
To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFNα in SLE and APS, and miRNAs are emerging as regulators of pDC activation.
Methods
miRNA and mRNA expression were measured by OpenArray and RNA-sequencing in pDCs of SLE, SLE + APS (APS secondary to SLE) and primary APS (PAPS) patients. The miRNA profile of patients was compared with the miRNA pattern of TLR7-activated pDCs.
Results
Among 131 miRNAs detected in pDCs, 35, 17 and 21 had a significantly lower level of expression in SLE, SLE + APS and PAPS patients, respectively, as compared with healthy controls (HC). Notably, the miRNA profile did not significantly differ between SLE and APS, but was driven by the presence or absence of an IFN signature. TLR7 stimulation induced a general downregulation of miRNAs, similar to the pattern observed in SLE and APS patients. miR-361-5p, miR-128-3p and miR-181a-2-3p expression was lower in patients with a high IFN signature (false discovery rate <0.05) as compared with patients with a low IFN signature and HCs. Pathway enrichment on the overlap of miRNA targets and upregulated genes from the RNAseq indicated that these miRNAs are involved in pDC activation and apoptosis.
Conclusion
Lower miRNA expression in pDCs is shared between SLE, SLE + APS and PAPS and is related to the IFN signature. As pDCs are the alleged source of the IFN signature in these patients, a better understanding of the molecular mechanisms/pathways leading to pDC dysregulation in SLE and APS might open novel pathways for therapeutic intervention.</description><subject>Adult</subject><subject>Antiphospholipid syndrome</subject><subject>Antiphospholipid Syndrome - genetics</subject><subject>Antiphospholipid Syndrome - metabolism</subject><subject>Apoptosis</subject><subject>Autoimmune diseases</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - metabolism</subject><subject>Dendritic Cells - pathology</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Interferon</subject><subject>Lupus</subject><subject>Lupus Erythematosus, Systemic - genetics</subject><subject>Lupus Erythematosus, Systemic - metabolism</subject><subject>Lupus Erythematosus, Systemic - pathology</subject><subject>Male</subject><subject>MicroRNAs</subject><subject>MicroRNAs - biosynthesis</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Molecular modelling</subject><subject>RNA, Messenger - genetics</subject><subject>Systemic lupus erythematosus</subject><subject>TLR7 protein</subject><subject>Toll-Like Receptor 7 - biosynthesis</subject><subject>Toll-Like Receptor 7 - genetics</subject><subject>Toll-like receptors</subject><subject>α-Interferon</subject><issn>1462-0324</issn><issn>1462-0332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkd1KJDEQhcOiqDv6BAtLgzfetCapTmZyKeL-gOyCeN9kOtVO3O6kzY_Sj7BvbYZRWbzaiyIJderjpA4hXxg9Z1TBRdhgHnXyg7-fL_7gzIT6RI5YI3lNAfje-503h-RzjA-UUsFgdUAOuVotYSnlEfk72i7421-XlfHPLuB9HnSy3lXWVdOg46i7OXlrKoPOBJtsV3U4DHHbty5h6DF4V08-lt4TVnGOCQuzGvKUY4VhThvcuozlpZ0pley08bHUYKcCjnMB-xGPyX6vh4gnr-eC3H27vrv6Ud_8_v7z6vKm7poVpNpIA0pxABQauDBSqgYAhGRqucY1ajBMaS6FZkYAGFxK1Us0XSeFgB4W5GyHnYJ_zBhTO9q4_ZJ26HNsedkRlc2K0iI9_SB98Dm4Yq7lQKVolCg-FgR2qrLHGAP27RTsqMPcMtpug2r_DardBVWmvr6y83pE8z7zlkwRnO8EPk__RXwBlJOogA</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>van den Hoogen, Lucas L</creator><creator>Rossato, Marzia</creator><creator>Lopes, Ana P</creator><creator>Pandit, Aridaman</creator><creator>Bekker, Cornelis P J</creator><creator>Fritsch-Stork, Ruth D E</creator><creator>van Roon, Joel A G</creator><creator>Radstake, Timothy R D J</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20180901</creationdate><title>microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome</title><author>van den Hoogen, Lucas L ; Rossato, Marzia ; Lopes, Ana P ; Pandit, Aridaman ; Bekker, Cornelis P J ; Fritsch-Stork, Ruth D E ; van Roon, Joel A G ; Radstake, Timothy R D J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-d6d399233e5a325d669433356197bebea3d19a265a1d533de769f6edcc6553f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Antiphospholipid syndrome</topic><topic>Antiphospholipid Syndrome - genetics</topic><topic>Antiphospholipid Syndrome - metabolism</topic><topic>Apoptosis</topic><topic>Autoimmune diseases</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - metabolism</topic><topic>Dendritic Cells - pathology</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Interferon</topic><topic>Lupus</topic><topic>Lupus Erythematosus, Systemic - genetics</topic><topic>Lupus Erythematosus, Systemic - metabolism</topic><topic>Lupus Erythematosus, Systemic - pathology</topic><topic>Male</topic><topic>MicroRNAs</topic><topic>MicroRNAs - biosynthesis</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Molecular modelling</topic><topic>RNA, Messenger - genetics</topic><topic>Systemic lupus erythematosus</topic><topic>TLR7 protein</topic><topic>Toll-Like Receptor 7 - biosynthesis</topic><topic>Toll-Like Receptor 7 - genetics</topic><topic>Toll-like receptors</topic><topic>α-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van den Hoogen, Lucas L</creatorcontrib><creatorcontrib>Rossato, Marzia</creatorcontrib><creatorcontrib>Lopes, Ana P</creatorcontrib><creatorcontrib>Pandit, Aridaman</creatorcontrib><creatorcontrib>Bekker, Cornelis P J</creatorcontrib><creatorcontrib>Fritsch-Stork, Ruth D E</creatorcontrib><creatorcontrib>van Roon, Joel A G</creatorcontrib><creatorcontrib>Radstake, Timothy R D J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Rheumatology (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van den Hoogen, Lucas L</au><au>Rossato, Marzia</au><au>Lopes, Ana P</au><au>Pandit, Aridaman</au><au>Bekker, Cornelis P J</au><au>Fritsch-Stork, Ruth D E</au><au>van Roon, Joel A G</au><au>Radstake, Timothy R D J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome</atitle><jtitle>Rheumatology (Oxford, England)</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>57</volume><issue>9</issue><spage>1669</spage><epage>1674</epage><pages>1669-1674</pages><issn>1462-0324</issn><eissn>1462-0332</eissn><abstract>Abstract
Objective
To investigate miRNA expression in relation to transcriptomic changes in plasmacytoid dendritic cells (pDCs) in SLE and APS. pDCs are major producers of IFNα in SLE and APS, and miRNAs are emerging as regulators of pDC activation.
Methods
miRNA and mRNA expression were measured by OpenArray and RNA-sequencing in pDCs of SLE, SLE + APS (APS secondary to SLE) and primary APS (PAPS) patients. The miRNA profile of patients was compared with the miRNA pattern of TLR7-activated pDCs.
Results
Among 131 miRNAs detected in pDCs, 35, 17 and 21 had a significantly lower level of expression in SLE, SLE + APS and PAPS patients, respectively, as compared with healthy controls (HC). Notably, the miRNA profile did not significantly differ between SLE and APS, but was driven by the presence or absence of an IFN signature. TLR7 stimulation induced a general downregulation of miRNAs, similar to the pattern observed in SLE and APS patients. miR-361-5p, miR-128-3p and miR-181a-2-3p expression was lower in patients with a high IFN signature (false discovery rate <0.05) as compared with patients with a low IFN signature and HCs. Pathway enrichment on the overlap of miRNA targets and upregulated genes from the RNAseq indicated that these miRNAs are involved in pDC activation and apoptosis.
Conclusion
Lower miRNA expression in pDCs is shared between SLE, SLE + APS and PAPS and is related to the IFN signature. As pDCs are the alleged source of the IFN signature in these patients, a better understanding of the molecular mechanisms/pathways leading to pDC dysregulation in SLE and APS might open novel pathways for therapeutic intervention.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>29873766</pmid><doi>10.1093/rheumatology/key159</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Adult Antiphospholipid syndrome Antiphospholipid Syndrome - genetics Antiphospholipid Syndrome - metabolism Apoptosis Autoimmune diseases Dendritic cells Dendritic Cells - metabolism Dendritic Cells - pathology Down-Regulation Female Gene expression Gene Expression Regulation Humans Interferon Lupus Lupus Erythematosus, Systemic - genetics Lupus Erythematosus, Systemic - metabolism Lupus Erythematosus, Systemic - pathology Male MicroRNAs MicroRNAs - biosynthesis MicroRNAs - genetics miRNA Molecular modelling RNA, Messenger - genetics Systemic lupus erythematosus TLR7 protein Toll-Like Receptor 7 - biosynthesis Toll-Like Receptor 7 - genetics Toll-like receptors α-Interferon |
| title | microRNA downregulation in plasmacytoid dendritic cells in interferon-positive systemic lupus erythematosus and antiphospholipid syndrome |
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