Lipocalin-2 Exacerbates Lupus Nephritis by Promoting Th1 Cell Differentiation
Lipocalin-2 (LCN2) is an indicator of the severity of lupus nephritis (LN) and plays a pivotal role in immune responses, but it is not known if its effect on LN pathogenesis derives from regulating the immune imbalance of T lymphocyte subsets. The expression of LCN2 in T cells and kidneys was assess...
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| Veröffentlicht in: | Journal of the American Society of Nephrology 2020-10, Vol.31 (10), p.2263-2277 |
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| creator | Chen, Weiwei Li, Wenchao Zhang, Zhuoya Tang, Xiaojun Wu, Shufang Yao, Genhong Li, Kang Wang, Dandan Xu, Yuemei Feng, Ruihai Duan, Xiaoxiao Fan, Xiangshan Lu, Liwei Chen, WanJun Li, Chaojun Sun, Lingyun |
| description | Lipocalin-2 (LCN2) is an indicator of the severity of lupus nephritis (LN) and plays a pivotal role in immune responses, but it is not known if its effect on LN pathogenesis derives from regulating the immune imbalance of T lymphocyte subsets.
The expression of LCN2 in T cells and kidneys was assessed in renal biopsies from patients with LN. We investigated the relationship between LCN2 levels and development of LN and systemic illness by injecting anti-LCN2 antibodies into MRL/
mice and analyzing pristane-treated
mice.
LCN2 is highly expressed in CD4
T cells and in renal tissues, and is associated with severe renal damage in patients with LN and in mice with experimental lupus. LCN2 promotes IFN-
overexpression in CD4
T cells through the IL-12/STAT4 pathway in an autocrine or paracrine manner. Both neutralization of LCN2 in MRL/
mice and genetic depletion of LCN2 in pristane-induced lupus mice greatly ameliorate nephritis. The frequency and number of splenic and renal Th1 cells decrease in proportion to LN disease activity. Conversely, administration of LCN2 exacerbates the disease with significantly higher renal activity scores and increased numbers of Th1 cells.
LCN2 plays a crucial role in Th1 cell differentiation, and may present a potential therapeutic target for LN. |
| doi_str_mv | 10.1681/asn.2019090937 |
| format | Article |
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The expression of LCN2 in T cells and kidneys was assessed in renal biopsies from patients with LN. We investigated the relationship between LCN2 levels and development of LN and systemic illness by injecting anti-LCN2 antibodies into MRL/
mice and analyzing pristane-treated
mice.
LCN2 is highly expressed in CD4
T cells and in renal tissues, and is associated with severe renal damage in patients with LN and in mice with experimental lupus. LCN2 promotes IFN-
overexpression in CD4
T cells through the IL-12/STAT4 pathway in an autocrine or paracrine manner. Both neutralization of LCN2 in MRL/
mice and genetic depletion of LCN2 in pristane-induced lupus mice greatly ameliorate nephritis. The frequency and number of splenic and renal Th1 cells decrease in proportion to LN disease activity. Conversely, administration of LCN2 exacerbates the disease with significantly higher renal activity scores and increased numbers of Th1 cells.
LCN2 plays a crucial role in Th1 cell differentiation, and may present a potential therapeutic target for LN.</description><identifier>ISSN: 1046-6673</identifier><identifier>EISSN: 1533-3450</identifier><identifier>DOI: 10.1681/asn.2019090937</identifier><identifier>PMID: 32646856</identifier><language>eng</language><publisher>United States: American Society of Nephrology</publisher><subject>Animals ; Basic Research ; Case-Control Studies ; Cell Differentiation ; Disease Models, Animal ; Female ; Humans ; Lipocalin-2 - metabolism ; Lupus Nephritis - etiology ; Lupus Nephritis - metabolism ; Lupus Nephritis - pathology ; Male ; Mice ; Mice, Inbred MRL lpr ; Th1 Cells - metabolism ; Th1 Cells - pathology</subject><ispartof>Journal of the American Society of Nephrology, 2020-10, Vol.31 (10), p.2263-2277</ispartof><rights>Copyright © 2020 by the American Society of Nephrology.</rights><rights>Copyright © 2020 by the American Society of Nephrology 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-5c767a924359181c3014825a7eb7f7d1d19eeb31588a610417d8056a852e0ff3</citedby><cites>FETCH-LOGICAL-c501t-5c767a924359181c3014825a7eb7f7d1d19eeb31588a610417d8056a852e0ff3</cites><orcidid>0000-0001-9474-7321 ; 0000-0001-8616-1419</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/PMC7609012/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609012/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32646856$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Weiwei</creatorcontrib><creatorcontrib>Li, Wenchao</creatorcontrib><creatorcontrib>Zhang, Zhuoya</creatorcontrib><creatorcontrib>Tang, Xiaojun</creatorcontrib><creatorcontrib>Wu, Shufang</creatorcontrib><creatorcontrib>Yao, Genhong</creatorcontrib><creatorcontrib>Li, Kang</creatorcontrib><creatorcontrib>Wang, Dandan</creatorcontrib><creatorcontrib>Xu, Yuemei</creatorcontrib><creatorcontrib>Feng, Ruihai</creatorcontrib><creatorcontrib>Duan, Xiaoxiao</creatorcontrib><creatorcontrib>Fan, Xiangshan</creatorcontrib><creatorcontrib>Lu, Liwei</creatorcontrib><creatorcontrib>Chen, WanJun</creatorcontrib><creatorcontrib>Li, Chaojun</creatorcontrib><creatorcontrib>Sun, Lingyun</creatorcontrib><title>Lipocalin-2 Exacerbates Lupus Nephritis by Promoting Th1 Cell Differentiation</title><title>Journal of the American Society of Nephrology</title><addtitle>J Am Soc Nephrol</addtitle><description>Lipocalin-2 (LCN2) is an indicator of the severity of lupus nephritis (LN) and plays a pivotal role in immune responses, but it is not known if its effect on LN pathogenesis derives from regulating the immune imbalance of T lymphocyte subsets.
The expression of LCN2 in T cells and kidneys was assessed in renal biopsies from patients with LN. We investigated the relationship between LCN2 levels and development of LN and systemic illness by injecting anti-LCN2 antibodies into MRL/
mice and analyzing pristane-treated
mice.
LCN2 is highly expressed in CD4
T cells and in renal tissues, and is associated with severe renal damage in patients with LN and in mice with experimental lupus. LCN2 promotes IFN-
overexpression in CD4
T cells through the IL-12/STAT4 pathway in an autocrine or paracrine manner. Both neutralization of LCN2 in MRL/
mice and genetic depletion of LCN2 in pristane-induced lupus mice greatly ameliorate nephritis. The frequency and number of splenic and renal Th1 cells decrease in proportion to LN disease activity. Conversely, administration of LCN2 exacerbates the disease with significantly higher renal activity scores and increased numbers of Th1 cells.
LCN2 plays a crucial role in Th1 cell differentiation, and may present a potential therapeutic target for LN.</description><subject>Animals</subject><subject>Basic Research</subject><subject>Case-Control Studies</subject><subject>Cell Differentiation</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Humans</subject><subject>Lipocalin-2 - metabolism</subject><subject>Lupus Nephritis - etiology</subject><subject>Lupus Nephritis - metabolism</subject><subject>Lupus Nephritis - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred MRL lpr</subject><subject>Th1 Cells - metabolism</subject><subject>Th1 Cells - pathology</subject><issn>1046-6673</issn><issn>1533-3450</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1PwzAMjRCIjcGVI-qRS0ecNEl3QZrG-JDKQGL3KG3TLahrStIi9u8J2viSD7bk52c_P4TOAY-Bp3ClfDMmGCY4BBUHaAiM0pgmDB-GGic85lzQATrx_hVjYESIYzSghCc8ZXyIHjPT2kLVpolJNP9QhXa56rSPsr7tfbTQ7dqZzvgo30bPzm5sZ5pVtFxDNNN1Hd2YqtJON51RnbHNKTqqVO312T6P0PJ2vpzdx9nT3cNsmsUFw9DFrBBcqAlJKJtACgXFkKSEKaFzUYkSSphonVNgaap4EAGiTDHjKmVE46qiI3S9o237fKPLIux3qpatMxvlttIqI_93GrOWK_suBQ9_AhIILvcEzr712ndyY3wRBKlG295LkhCKOWeCB-h4By2c9d7p6mcNYPllgZy-LOSvBWHg4u9xP_Dvn9NPOv2Bjg</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Chen, Weiwei</creator><creator>Li, Wenchao</creator><creator>Zhang, Zhuoya</creator><creator>Tang, Xiaojun</creator><creator>Wu, Shufang</creator><creator>Yao, Genhong</creator><creator>Li, Kang</creator><creator>Wang, Dandan</creator><creator>Xu, Yuemei</creator><creator>Feng, Ruihai</creator><creator>Duan, Xiaoxiao</creator><creator>Fan, Xiangshan</creator><creator>Lu, Liwei</creator><creator>Chen, WanJun</creator><creator>Li, Chaojun</creator><creator>Sun, Lingyun</creator><general>American Society of Nephrology</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9474-7321</orcidid><orcidid>https://orcid.org/0000-0001-8616-1419</orcidid></search><sort><creationdate>20201001</creationdate><title>Lipocalin-2 Exacerbates Lupus Nephritis by Promoting Th1 Cell Differentiation</title><author>Chen, Weiwei ; Li, Wenchao ; Zhang, Zhuoya ; Tang, Xiaojun ; Wu, Shufang ; Yao, Genhong ; Li, Kang ; Wang, Dandan ; Xu, Yuemei ; Feng, Ruihai ; Duan, Xiaoxiao ; Fan, Xiangshan ; Lu, Liwei ; Chen, WanJun ; Li, Chaojun ; Sun, Lingyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-5c767a924359181c3014825a7eb7f7d1d19eeb31588a610417d8056a852e0ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Basic Research</topic><topic>Case-Control Studies</topic><topic>Cell Differentiation</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Humans</topic><topic>Lipocalin-2 - metabolism</topic><topic>Lupus Nephritis - etiology</topic><topic>Lupus Nephritis - metabolism</topic><topic>Lupus Nephritis - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred MRL lpr</topic><topic>Th1 Cells - metabolism</topic><topic>Th1 Cells - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Weiwei</creatorcontrib><creatorcontrib>Li, Wenchao</creatorcontrib><creatorcontrib>Zhang, Zhuoya</creatorcontrib><creatorcontrib>Tang, Xiaojun</creatorcontrib><creatorcontrib>Wu, Shufang</creatorcontrib><creatorcontrib>Yao, Genhong</creatorcontrib><creatorcontrib>Li, Kang</creatorcontrib><creatorcontrib>Wang, Dandan</creatorcontrib><creatorcontrib>Xu, Yuemei</creatorcontrib><creatorcontrib>Feng, Ruihai</creatorcontrib><creatorcontrib>Duan, Xiaoxiao</creatorcontrib><creatorcontrib>Fan, Xiangshan</creatorcontrib><creatorcontrib>Lu, Liwei</creatorcontrib><creatorcontrib>Chen, WanJun</creatorcontrib><creatorcontrib>Li, Chaojun</creatorcontrib><creatorcontrib>Sun, Lingyun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Society of Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Weiwei</au><au>Li, Wenchao</au><au>Zhang, Zhuoya</au><au>Tang, Xiaojun</au><au>Wu, Shufang</au><au>Yao, Genhong</au><au>Li, Kang</au><au>Wang, Dandan</au><au>Xu, Yuemei</au><au>Feng, Ruihai</au><au>Duan, Xiaoxiao</au><au>Fan, Xiangshan</au><au>Lu, Liwei</au><au>Chen, WanJun</au><au>Li, Chaojun</au><au>Sun, Lingyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipocalin-2 Exacerbates Lupus Nephritis by Promoting Th1 Cell Differentiation</atitle><jtitle>Journal of the American Society of Nephrology</jtitle><addtitle>J Am Soc Nephrol</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>31</volume><issue>10</issue><spage>2263</spage><epage>2277</epage><pages>2263-2277</pages><issn>1046-6673</issn><eissn>1533-3450</eissn><abstract>Lipocalin-2 (LCN2) is an indicator of the severity of lupus nephritis (LN) and plays a pivotal role in immune responses, but it is not known if its effect on LN pathogenesis derives from regulating the immune imbalance of T lymphocyte subsets.
The expression of LCN2 in T cells and kidneys was assessed in renal biopsies from patients with LN. We investigated the relationship between LCN2 levels and development of LN and systemic illness by injecting anti-LCN2 antibodies into MRL/
mice and analyzing pristane-treated
mice.
LCN2 is highly expressed in CD4
T cells and in renal tissues, and is associated with severe renal damage in patients with LN and in mice with experimental lupus. LCN2 promotes IFN-
overexpression in CD4
T cells through the IL-12/STAT4 pathway in an autocrine or paracrine manner. Both neutralization of LCN2 in MRL/
mice and genetic depletion of LCN2 in pristane-induced lupus mice greatly ameliorate nephritis. The frequency and number of splenic and renal Th1 cells decrease in proportion to LN disease activity. Conversely, administration of LCN2 exacerbates the disease with significantly higher renal activity scores and increased numbers of Th1 cells.
LCN2 plays a crucial role in Th1 cell differentiation, and may present a potential therapeutic target for LN.</abstract><cop>United States</cop><pub>American Society of Nephrology</pub><pmid>32646856</pmid><doi>10.1681/asn.2019090937</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-9474-7321</orcidid><orcidid>https://orcid.org/0000-0001-8616-1419</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Basic Research Case-Control Studies Cell Differentiation Disease Models, Animal Female Humans Lipocalin-2 - metabolism Lupus Nephritis - etiology Lupus Nephritis - metabolism Lupus Nephritis - pathology Male Mice Mice, Inbred MRL lpr Th1 Cells - metabolism Th1 Cells - pathology |
| title | Lipocalin-2 Exacerbates Lupus Nephritis by Promoting Th1 Cell Differentiation |
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