DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8
Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits pot...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2024-02, Vol.121 (7), p.e2310264121 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 7 |
| container_start_page | e2310264121 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 121 |
| creator | Swarnkar, Gaurav Semenkovich, Nicholas P Arra, Manoj Mims, Dorothy K Naqvi, Syeda Kanwal Peterson, Timothy Mbalaviele, Gabriel Wu, Chia-Lung Abu-Amer, Yousef |
| description | Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the transcription factor Irf8 (interferon regulatory factor 8) induced its re-expression and promoted its repressor activity. As a result, DAC restored joint homeostasis by resetting the transcriptomic signature of negative regulators of inflammation in synovial macrophages (MerTK, Trem2, and Cx3cr1), T
(Foxp3), and SFs (Pdpn and Fapα). In conclusion, we found that Irf8 is necessary for the inhibitory effect of DAC in murine arthritis and that direct expression of Irf8 is sufficient to significantly mitigate arthritis. |
| doi_str_mv | 10.1073/pnas.2310264121 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10873594</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2923324191</sourcerecordid><originalsourceid>FETCH-LOGICAL-c381t-6631ff81360043ca5a2faab76ce1f93da5ab3d0b5a87136c556221c0db65c5d53</originalsourceid><addsrcrecordid>eNpdkctr3DAQxkVpabbbnnMrhl5ycaKHJVunEDZ9QWgv7VmMZWlXiS1tJDng_74ySdPHaWDm933MzIfQKcHnBLfs4ughnVNGMBUNoeQF2hAsSS0aiV-iDca0rbuGNifoTUq3GGPJO_wanbCOESkF26C7629X1WE5hsnkwzJCdsFXMJnRhQjZpMrEkNyDqZy3I0wT5BCXCmI-RJddqvqlmsIwr0K_L1A20RaJr6LZr92VtqBLrbu36JWFMZl3T3WLfn76-GP3pb75_vnr7uqm1qwjuRaCEWs7wgTGDdPAgVqAvhXaECvZUBo9G3DPoWsLpDkXlBKNh15wzQfOtujy0fc495MZtPE5wqiO0U0QFxXAqX8n3h3UPjwogruWcdkUh7MnhxjuZ5OymlzSZhzBmzAnRSVljDZEkoJ--A-9DXP05b6Vann5fmG36OKR0uWdKRr7vA3Bak1SrUmqP0kWxfu_j3jmf0fHfgGMqp07</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2927542423</pqid></control><display><type>article</type><title>DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Swarnkar, Gaurav ; Semenkovich, Nicholas P ; Arra, Manoj ; Mims, Dorothy K ; Naqvi, Syeda Kanwal ; Peterson, Timothy ; Mbalaviele, Gabriel ; Wu, Chia-Lung ; Abu-Amer, Yousef</creator><creatorcontrib>Swarnkar, Gaurav ; Semenkovich, Nicholas P ; Arra, Manoj ; Mims, Dorothy K ; Naqvi, Syeda Kanwal ; Peterson, Timothy ; Mbalaviele, Gabriel ; Wu, Chia-Lung ; Abu-Amer, Yousef</creatorcontrib><description>Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the transcription factor Irf8 (interferon regulatory factor 8) induced its re-expression and promoted its repressor activity. As a result, DAC restored joint homeostasis by resetting the transcriptomic signature of negative regulators of inflammation in synovial macrophages (MerTK, Trem2, and Cx3cr1), T
(Foxp3), and SFs (Pdpn and Fapα). In conclusion, we found that Irf8 is necessary for the inhibitory effect of DAC in murine arthritis and that direct expression of Irf8 is sufficient to significantly mitigate arthritis.</description><identifier>ISSN: 0027-8424</identifier><identifier>ISSN: 1091-6490</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2310264121</identifier><identifier>PMID: 38319963</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>5-aza-2'-deoxycytidine ; Animal diseases ; Animal models ; Animals ; Anti-Inflammatory Agents ; Arthritis ; Arthritis - genetics ; Autoimmune diseases ; Azacitidine - pharmacology ; Biological Sciences ; Cell differentiation ; CpG islands ; CX3CR1 protein ; Cytosine ; Decitabine - pharmacology ; Demethylation ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Epigenesis, Genetic ; Epigenetics ; Foxp3 protein ; Homeostasis ; Immunoregulation ; Inflammation - genetics ; Interferon ; Interferon regulatory factor ; Interferon Regulatory Factors - metabolism ; Lymphocytes ; Lymphocytes T ; Macrophages ; Membrane Glycoproteins - metabolism ; Mice ; Pathogenesis ; Receptors, Immunologic - genetics ; Signs and symptoms ; Transcriptomics</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2024-02, Vol.121 (7), p.e2310264121</ispartof><rights>Copyright National Academy of Sciences Feb 13, 2024</rights><rights>Copyright © 2024 the Author(s). Published by PNAS. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-6631ff81360043ca5a2faab76ce1f93da5ab3d0b5a87136c556221c0db65c5d53</citedby><cites>FETCH-LOGICAL-c381t-6631ff81360043ca5a2faab76ce1f93da5ab3d0b5a87136c556221c0db65c5d53</cites><orcidid>0000-0001-6052-4971 ; 0000-0002-5890-5086 ; 0000-0002-0618-6649 ; 0000-0001-5266-6734 ; 0000-0001-9598-7036 ; 0000-0003-4660-0952</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873594/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873594/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38319963$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Swarnkar, Gaurav</creatorcontrib><creatorcontrib>Semenkovich, Nicholas P</creatorcontrib><creatorcontrib>Arra, Manoj</creatorcontrib><creatorcontrib>Mims, Dorothy K</creatorcontrib><creatorcontrib>Naqvi, Syeda Kanwal</creatorcontrib><creatorcontrib>Peterson, Timothy</creatorcontrib><creatorcontrib>Mbalaviele, Gabriel</creatorcontrib><creatorcontrib>Wu, Chia-Lung</creatorcontrib><creatorcontrib>Abu-Amer, Yousef</creatorcontrib><title>DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the transcription factor Irf8 (interferon regulatory factor 8) induced its re-expression and promoted its repressor activity. As a result, DAC restored joint homeostasis by resetting the transcriptomic signature of negative regulators of inflammation in synovial macrophages (MerTK, Trem2, and Cx3cr1), T
(Foxp3), and SFs (Pdpn and Fapα). In conclusion, we found that Irf8 is necessary for the inhibitory effect of DAC in murine arthritis and that direct expression of Irf8 is sufficient to significantly mitigate arthritis.</description><subject>5-aza-2'-deoxycytidine</subject><subject>Animal diseases</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents</subject><subject>Arthritis</subject><subject>Arthritis - genetics</subject><subject>Autoimmune diseases</subject><subject>Azacitidine - pharmacology</subject><subject>Biological Sciences</subject><subject>Cell differentiation</subject><subject>CpG islands</subject><subject>CX3CR1 protein</subject><subject>Cytosine</subject><subject>Decitabine - pharmacology</subject><subject>Demethylation</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Foxp3 protein</subject><subject>Homeostasis</subject><subject>Immunoregulation</subject><subject>Inflammation - genetics</subject><subject>Interferon</subject><subject>Interferon regulatory factor</subject><subject>Interferon Regulatory Factors - metabolism</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Pathogenesis</subject><subject>Receptors, Immunologic - genetics</subject><subject>Signs and symptoms</subject><subject>Transcriptomics</subject><issn>0027-8424</issn><issn>1091-6490</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctr3DAQxkVpabbbnnMrhl5ycaKHJVunEDZ9QWgv7VmMZWlXiS1tJDng_74ySdPHaWDm933MzIfQKcHnBLfs4ughnVNGMBUNoeQF2hAsSS0aiV-iDca0rbuGNifoTUq3GGPJO_wanbCOESkF26C7629X1WE5hsnkwzJCdsFXMJnRhQjZpMrEkNyDqZy3I0wT5BCXCmI-RJddqvqlmsIwr0K_L1A20RaJr6LZr92VtqBLrbu36JWFMZl3T3WLfn76-GP3pb75_vnr7uqm1qwjuRaCEWs7wgTGDdPAgVqAvhXaECvZUBo9G3DPoWsLpDkXlBKNh15wzQfOtujy0fc495MZtPE5wqiO0U0QFxXAqX8n3h3UPjwogruWcdkUh7MnhxjuZ5OymlzSZhzBmzAnRSVljDZEkoJ--A-9DXP05b6Vann5fmG36OKR0uWdKRr7vA3Bak1SrUmqP0kWxfu_j3jmf0fHfgGMqp07</recordid><startdate>20240213</startdate><enddate>20240213</enddate><creator>Swarnkar, Gaurav</creator><creator>Semenkovich, Nicholas P</creator><creator>Arra, Manoj</creator><creator>Mims, Dorothy K</creator><creator>Naqvi, Syeda Kanwal</creator><creator>Peterson, Timothy</creator><creator>Mbalaviele, Gabriel</creator><creator>Wu, Chia-Lung</creator><creator>Abu-Amer, Yousef</creator><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6052-4971</orcidid><orcidid>https://orcid.org/0000-0002-5890-5086</orcidid><orcidid>https://orcid.org/0000-0002-0618-6649</orcidid><orcidid>https://orcid.org/0000-0001-5266-6734</orcidid><orcidid>https://orcid.org/0000-0001-9598-7036</orcidid><orcidid>https://orcid.org/0000-0003-4660-0952</orcidid></search><sort><creationdate>20240213</creationdate><title>DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8</title><author>Swarnkar, Gaurav ; Semenkovich, Nicholas P ; Arra, Manoj ; Mims, Dorothy K ; Naqvi, Syeda Kanwal ; Peterson, Timothy ; Mbalaviele, Gabriel ; Wu, Chia-Lung ; Abu-Amer, Yousef</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-6631ff81360043ca5a2faab76ce1f93da5ab3d0b5a87136c556221c0db65c5d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>5-aza-2'-deoxycytidine</topic><topic>Animal diseases</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents</topic><topic>Arthritis</topic><topic>Arthritis - genetics</topic><topic>Autoimmune diseases</topic><topic>Azacitidine - pharmacology</topic><topic>Biological Sciences</topic><topic>Cell differentiation</topic><topic>CpG islands</topic><topic>CX3CR1 protein</topic><topic>Cytosine</topic><topic>Decitabine - pharmacology</topic><topic>Demethylation</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Foxp3 protein</topic><topic>Homeostasis</topic><topic>Immunoregulation</topic><topic>Inflammation - genetics</topic><topic>Interferon</topic><topic>Interferon regulatory factor</topic><topic>Interferon Regulatory Factors - metabolism</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mice</topic><topic>Pathogenesis</topic><topic>Receptors, Immunologic - genetics</topic><topic>Signs and symptoms</topic><topic>Transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Swarnkar, Gaurav</creatorcontrib><creatorcontrib>Semenkovich, Nicholas P</creatorcontrib><creatorcontrib>Arra, Manoj</creatorcontrib><creatorcontrib>Mims, Dorothy K</creatorcontrib><creatorcontrib>Naqvi, Syeda Kanwal</creatorcontrib><creatorcontrib>Peterson, Timothy</creatorcontrib><creatorcontrib>Mbalaviele, Gabriel</creatorcontrib><creatorcontrib>Wu, Chia-Lung</creatorcontrib><creatorcontrib>Abu-Amer, Yousef</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Swarnkar, Gaurav</au><au>Semenkovich, Nicholas P</au><au>Arra, Manoj</au><au>Mims, Dorothy K</au><au>Naqvi, Syeda Kanwal</au><au>Peterson, Timothy</au><au>Mbalaviele, Gabriel</au><au>Wu, Chia-Lung</au><au>Abu-Amer, Yousef</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2024-02-13</date><risdate>2024</risdate><volume>121</volume><issue>7</issue><spage>e2310264121</spage><pages>e2310264121-</pages><issn>0027-8424</issn><issn>1091-6490</issn><eissn>1091-6490</eissn><abstract>Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the transcription factor Irf8 (interferon regulatory factor 8) induced its re-expression and promoted its repressor activity. As a result, DAC restored joint homeostasis by resetting the transcriptomic signature of negative regulators of inflammation in synovial macrophages (MerTK, Trem2, and Cx3cr1), T
(Foxp3), and SFs (Pdpn and Fapα). In conclusion, we found that Irf8 is necessary for the inhibitory effect of DAC in murine arthritis and that direct expression of Irf8 is sufficient to significantly mitigate arthritis.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>38319963</pmid><doi>10.1073/pnas.2310264121</doi><orcidid>https://orcid.org/0000-0001-6052-4971</orcidid><orcidid>https://orcid.org/0000-0002-5890-5086</orcidid><orcidid>https://orcid.org/0000-0002-0618-6649</orcidid><orcidid>https://orcid.org/0000-0001-5266-6734</orcidid><orcidid>https://orcid.org/0000-0001-9598-7036</orcidid><orcidid>https://orcid.org/0000-0003-4660-0952</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2024-02, Vol.121 (7), p.e2310264121 |
| issn | 0027-8424 1091-6490 1091-6490 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10873594 |
| source | MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | 5-aza-2'-deoxycytidine Animal diseases Animal models Animals Anti-Inflammatory Agents Arthritis Arthritis - genetics Autoimmune diseases Azacitidine - pharmacology Biological Sciences Cell differentiation CpG islands CX3CR1 protein Cytosine Decitabine - pharmacology Demethylation Deoxyribonucleic acid DNA DNA Methylation Epigenesis, Genetic Epigenetics Foxp3 protein Homeostasis Immunoregulation Inflammation - genetics Interferon Interferon regulatory factor Interferon Regulatory Factors - metabolism Lymphocytes Lymphocytes T Macrophages Membrane Glycoproteins - metabolism Mice Pathogenesis Receptors, Immunologic - genetics Signs and symptoms Transcriptomics |
| title | DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T00%3A55%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DNA%20hypomethylation%20ameliorates%20erosive%20inflammatory%20arthritis%20by%20modulating%20interferon%20regulatory%20factor-8&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Swarnkar,%20Gaurav&rft.date=2024-02-13&rft.volume=121&rft.issue=7&rft.spage=e2310264121&rft.pages=e2310264121-&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.2310264121&rft_dat=%3Cproquest_pubme%3E2923324191%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2927542423&rft_id=info:pmid/38319963&rfr_iscdi=true |