Dexamethasone reduces autoantibody levels in MRL/lpr mice by inhibiting Tfh cell responses
Previous studies have shown that dexamethasone (Dex) reduces the levels of anti‐nuclear (ANA) and anti‐dsDNA antibodies in MRL/lpr mice (a mouse model of SLE). However, the effect of Dex on T follicular helper (Tfh) cells is less documented. Here, using the MRL/lpr mouse model, we investigated the i...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2021-09, Vol.25 (17), p.8329-8337 |
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| creator | Shen, Chunxiu Xue, Xiaonan Zhang, Xiaoyu Wu, Lihua Duan, Xiangguo Su, Chunxia |
| description | Previous studies have shown that dexamethasone (Dex) reduces the levels of anti‐nuclear (ANA) and anti‐dsDNA antibodies in MRL/lpr mice (a mouse model of SLE). However, the effect of Dex on T follicular helper (Tfh) cells is less documented. Here, using the MRL/lpr mouse model, we investigated the influence of Dex on Tfh cells and potential underlying mechanisms. The data showed that the proportion of Tfh cells, identified as CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+ cells, markedly decreased after treatment with the Dex, in both Balb/c mice and MRL/lpr mice. Dex significantly inhibited IL‐21 expression at both the mRNA and the protein levels. Dex also significantly reduced the proportion of germinal centre B cells and decreased serum IgG, IgG2a/b and IgA levels. Moreover, a positive correlation between the proportion of Tfh cells (CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+) and autoantibodies was observed. Dex significantly increased the Prdm1 and Stat5b mRNA expression and decreased the Bcl‐6 and c‐Maf mRNA expression of CD4+T cells. In brief, Dex inhibited the Tfh development, which relies on many other transcription factors in addition to Bcl‐6. Our data indicate that Dex can be used as a Tfh cell inhibitor in SLE. |
| doi_str_mv | 10.1111/jcmm.16785 |
| format | Article |
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However, the effect of Dex on T follicular helper (Tfh) cells is less documented. Here, using the MRL/lpr mouse model, we investigated the influence of Dex on Tfh cells and potential underlying mechanisms. The data showed that the proportion of Tfh cells, identified as CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+ cells, markedly decreased after treatment with the Dex, in both Balb/c mice and MRL/lpr mice. Dex significantly inhibited IL‐21 expression at both the mRNA and the protein levels. Dex also significantly reduced the proportion of germinal centre B cells and decreased serum IgG, IgG2a/b and IgA levels. Moreover, a positive correlation between the proportion of Tfh cells (CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+) and autoantibodies was observed. Dex significantly increased the Prdm1 and Stat5b mRNA expression and decreased the Bcl‐6 and c‐Maf mRNA expression of CD4+T cells. In brief, Dex inhibited the Tfh development, which relies on many other transcription factors in addition to Bcl‐6. Our data indicate that Dex can be used as a Tfh cell inhibitor in SLE.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.16785</identifier><identifier>PMID: 34318604</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Animals ; Anti-Inflammatory Agents - pharmacology ; Antibodies ; Autoantibodies ; B-Lymphocytes - cytology ; B-Lymphocytes - drug effects ; B-Lymphocytes - immunology ; CD4 antigen ; Cell growth ; CXCR5 protein ; Cytokines ; Dexamethasone ; dexamethasone (Dex) ; Dexamethasone - pharmacology ; Female ; Flow cytometry ; Gene expression ; Immunoglobulin A ; Immunoglobulin G ; Laboratory animals ; Lupus ; Lupus Erythematosus, Systemic - drug therapy ; Lupus Erythematosus, Systemic - immunology ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Mice ; Mice, Inbred BALB C ; Mice, Inbred MRL lpr ; MRL/lpr mice ; Original ; Quantitative analysis ; SLE ; Steroids ; T follicular helper (Tfh) cells ; T Follicular Helper Cells - cytology ; T Follicular Helper Cells - drug effects ; T Follicular Helper Cells - immunology ; Transcription factors</subject><ispartof>Journal of cellular and molecular medicine, 2021-09, Vol.25 (17), p.8329-8337</ispartof><rights>2021 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4485-198e6954e8f1c87ed538cb1fd8ae26e8e934b1ced9b971495208632fe1c37cef3</citedby><cites>FETCH-LOGICAL-c4485-198e6954e8f1c87ed538cb1fd8ae26e8e934b1ced9b971495208632fe1c37cef3</cites><orcidid>0000-0002-8320-7220</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/PMC8419171/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419171/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34318604$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shen, Chunxiu</creatorcontrib><creatorcontrib>Xue, Xiaonan</creatorcontrib><creatorcontrib>Zhang, Xiaoyu</creatorcontrib><creatorcontrib>Wu, Lihua</creatorcontrib><creatorcontrib>Duan, Xiangguo</creatorcontrib><creatorcontrib>Su, Chunxia</creatorcontrib><title>Dexamethasone reduces autoantibody levels in MRL/lpr mice by inhibiting Tfh cell responses</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>Previous studies have shown that dexamethasone (Dex) reduces the levels of anti‐nuclear (ANA) and anti‐dsDNA antibodies in MRL/lpr mice (a mouse model of SLE). However, the effect of Dex on T follicular helper (Tfh) cells is less documented. Here, using the MRL/lpr mouse model, we investigated the influence of Dex on Tfh cells and potential underlying mechanisms. The data showed that the proportion of Tfh cells, identified as CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+ cells, markedly decreased after treatment with the Dex, in both Balb/c mice and MRL/lpr mice. Dex significantly inhibited IL‐21 expression at both the mRNA and the protein levels. Dex also significantly reduced the proportion of germinal centre B cells and decreased serum IgG, IgG2a/b and IgA levels. Moreover, a positive correlation between the proportion of Tfh cells (CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+) and autoantibodies was observed. Dex significantly increased the Prdm1 and Stat5b mRNA expression and decreased the Bcl‐6 and c‐Maf mRNA expression of CD4+T cells. In brief, Dex inhibited the Tfh development, which relies on many other transcription factors in addition to Bcl‐6. Our data indicate that Dex can be used as a Tfh cell inhibitor in SLE.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Antibodies</subject><subject>Autoantibodies</subject><subject>B-Lymphocytes - cytology</subject><subject>B-Lymphocytes - drug effects</subject><subject>B-Lymphocytes - immunology</subject><subject>CD4 antigen</subject><subject>Cell growth</subject><subject>CXCR5 protein</subject><subject>Cytokines</subject><subject>Dexamethasone</subject><subject>dexamethasone (Dex)</subject><subject>Dexamethasone - pharmacology</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin G</subject><subject>Laboratory animals</subject><subject>Lupus</subject><subject>Lupus Erythematosus, Systemic - drug therapy</subject><subject>Lupus Erythematosus, Systemic - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred MRL lpr</subject><subject>MRL/lpr mice</subject><subject>Original</subject><subject>Quantitative analysis</subject><subject>SLE</subject><subject>Steroids</subject><subject>T follicular helper (Tfh) cells</subject><subject>T Follicular Helper Cells - cytology</subject><subject>T Follicular Helper Cells - drug effects</subject><subject>T Follicular Helper Cells - immunology</subject><subject>Transcription factors</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUFrFDEYhoNYbK1e_AES8CLCtvNNkpnkIshatWUXQerFS8hkvulmmUm2yUzt_nuz7raoB3NJ-PLw8L28hLyC4gzyOV_bYTiDqpbiCTkBIcsZV4w_PbxBMnlMnqe0LgpWAVPPyDHjDGRV8BPy4yPemwHHlUnBI43YThYTNdMYjB9dE9ot7fEO-0Sdp8tvi_N-E-ngLNJmm0cr17jR-Rt63a2oxb7PirQJPmF6QY460yd8ebhPyfdPF9fzL7PF18-X8w-LmeVcihkoiZUSHGUHVtbYCiZtA10rDZYVSsxZGrDYqkbVwJUoC1mxskOwrLbYsVPyfu_dTM2ArUU_RtPrTXSDiVsdjNN__3i30jfhTksOCmrIgrcHQQy3E6ZRDy7tshiPYUq6FEKoSpaSZ_TNP-g6TNHneJmqVFkrVuyod3vKxpBSxO5xGSj0rjK9q0z_rizDr_9c_xF96CgDsAd-uh63_1Hpq_lyuZf-Auw8orU</recordid><startdate>202109</startdate><enddate>202109</enddate><creator>Shen, Chunxiu</creator><creator>Xue, Xiaonan</creator><creator>Zhang, Xiaoyu</creator><creator>Wu, Lihua</creator><creator>Duan, Xiangguo</creator><creator>Su, Chunxia</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8320-7220</orcidid></search><sort><creationdate>202109</creationdate><title>Dexamethasone reduces autoantibody levels in MRL/lpr mice by inhibiting Tfh cell responses</title><author>Shen, Chunxiu ; Xue, Xiaonan ; Zhang, Xiaoyu ; Wu, Lihua ; Duan, Xiangguo ; Su, Chunxia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4485-198e6954e8f1c87ed538cb1fd8ae26e8e934b1ced9b971495208632fe1c37cef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Antibodies</topic><topic>Autoantibodies</topic><topic>B-Lymphocytes - cytology</topic><topic>B-Lymphocytes - drug effects</topic><topic>B-Lymphocytes - immunology</topic><topic>CD4 antigen</topic><topic>Cell growth</topic><topic>CXCR5 protein</topic><topic>Cytokines</topic><topic>Dexamethasone</topic><topic>dexamethasone (Dex)</topic><topic>Dexamethasone - pharmacology</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin G</topic><topic>Laboratory animals</topic><topic>Lupus</topic><topic>Lupus Erythematosus, Systemic - drug therapy</topic><topic>Lupus Erythematosus, Systemic - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred MRL lpr</topic><topic>MRL/lpr mice</topic><topic>Original</topic><topic>Quantitative analysis</topic><topic>SLE</topic><topic>Steroids</topic><topic>T follicular helper (Tfh) cells</topic><topic>T Follicular Helper Cells - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular and molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shen, Chunxiu</au><au>Xue, Xiaonan</au><au>Zhang, Xiaoyu</au><au>Wu, Lihua</au><au>Duan, Xiangguo</au><au>Su, Chunxia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dexamethasone reduces autoantibody levels in MRL/lpr mice by inhibiting Tfh cell responses</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2021-09</date><risdate>2021</risdate><volume>25</volume><issue>17</issue><spage>8329</spage><epage>8337</epage><pages>8329-8337</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract>Previous studies have shown that dexamethasone (Dex) reduces the levels of anti‐nuclear (ANA) and anti‐dsDNA antibodies in MRL/lpr mice (a mouse model of SLE). However, the effect of Dex on T follicular helper (Tfh) cells is less documented. Here, using the MRL/lpr mouse model, we investigated the influence of Dex on Tfh cells and potential underlying mechanisms. The data showed that the proportion of Tfh cells, identified as CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+ cells, markedly decreased after treatment with the Dex, in both Balb/c mice and MRL/lpr mice. Dex significantly inhibited IL‐21 expression at both the mRNA and the protein levels. Dex also significantly reduced the proportion of germinal centre B cells and decreased serum IgG, IgG2a/b and IgA levels. Moreover, a positive correlation between the proportion of Tfh cells (CD4+CXCR5+ICOS+, CD4+CXCR5+PD‐1+ or CD4+BCL‐6+) and autoantibodies was observed. Dex significantly increased the Prdm1 and Stat5b mRNA expression and decreased the Bcl‐6 and c‐Maf mRNA expression of CD4+T cells. In brief, Dex inhibited the Tfh development, which relies on many other transcription factors in addition to Bcl‐6. Our data indicate that Dex can be used as a Tfh cell inhibitor in SLE.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>34318604</pmid><doi>10.1111/jcmm.16785</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-8320-7220</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents - pharmacology Antibodies Autoantibodies B-Lymphocytes - cytology B-Lymphocytes - drug effects B-Lymphocytes - immunology CD4 antigen Cell growth CXCR5 protein Cytokines Dexamethasone dexamethasone (Dex) Dexamethasone - pharmacology Female Flow cytometry Gene expression Immunoglobulin A Immunoglobulin G Laboratory animals Lupus Lupus Erythematosus, Systemic - drug therapy Lupus Erythematosus, Systemic - immunology Lymphocytes Lymphocytes B Lymphocytes T Mice Mice, Inbred BALB C Mice, Inbred MRL lpr MRL/lpr mice Original Quantitative analysis SLE Steroids T follicular helper (Tfh) cells T Follicular Helper Cells - cytology T Follicular Helper Cells - drug effects T Follicular Helper Cells - immunology Transcription factors |
| title | Dexamethasone reduces autoantibody levels in MRL/lpr mice by inhibiting Tfh cell responses |
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