An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1
Thymocyte antigen-1 (THY-1)is a potential target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate RA progression. In this study, we screened an antibody targeting T...
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Veröffentlicht in: | Experimental cell research 2023-03, Vol.424 (1), p.113490-113490, Article 113490 |
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creator | Hu, Xuanxuan Li, Meiqi Zhang, Yu Sang, Kanru Zhang, Yejun Li, Wulan Liu, Bo Wan, Leyu Du, Bang Qian, Jinheng Meng, Fanxi Fu, Yanneng Dai, Meijuan Gao, Guohui Ye, Hui |
description | Thymocyte antigen-1 (THY-1)is a potential target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate RA progression. In this study, we screened an antibody targeting THY-1 (THY-1 Ab) and explored its mechanism in alleviating RA progression. THY-1 Ab was screened from ScFv phage antibody library by phage display technology (PDT). THY-1 Ab–treated collagen induced arthritis (CIA) mice had lower degree of arthritis scores. We explore the mechanism of THY-1 Ab in alleviating RA progression. THY-1 Ab can remarkably inhibit the secretion of pro-inflammatory factors and promote the secretion of anti-inflammatory factors. Further experiments showed that THY1 Ab downregulated the expression of JUNB by the hsa_circ_0094342/miRNA-155–5P/SPI1 axis, inhibited RA angiogenesis and osteoclast differentiation, and relieved RA progression. These findings support that THY-1 Ab is a promising therapeutic antibody for RA treatment. |
doi_str_mv | 10.1016/j.yexcr.2023.113490 |
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In this study, we screened an antibody targeting THY-1 (THY-1 Ab) and explored its mechanism in alleviating RA progression. THY-1 Ab was screened from ScFv phage antibody library by phage display technology (PDT). THY-1 Ab–treated collagen induced arthritis (CIA) mice had lower degree of arthritis scores. We explore the mechanism of THY-1 Ab in alleviating RA progression. THY-1 Ab can remarkably inhibit the secretion of pro-inflammatory factors and promote the secretion of anti-inflammatory factors. Further experiments showed that THY1 Ab downregulated the expression of JUNB by the hsa_circ_0094342/miRNA-155–5P/SPI1 axis, inhibited RA angiogenesis and osteoclast differentiation, and relieved RA progression. These findings support that THY-1 Ab is a promising therapeutic antibody for RA treatment.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1016/j.yexcr.2023.113490</identifier><identifier>PMID: 36706943</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Angiogenesis ; Animals ; Antigens - immunology ; Arthritis, Experimental - metabolism ; Arthritis, Experimental - therapy ; Arthritis, Rheumatoid - metabolism ; Arthritis, Rheumatoid - therapy ; Cell Proliferation ; Cells, Cultured ; Fibroblasts - metabolism ; Humans ; Immunotherapy ; Mice ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Osteoclast differentiation ; Osteoclasts - metabolism ; Phage display technology ; Rheumatoid arthritis ; Synovial Membrane - metabolism ; THY-1 Ab ; Thymocytes - metabolism</subject><ispartof>Experimental cell research, 2023-03, Vol.424 (1), p.113490-113490, Article 113490</ispartof><rights>2023 The Authors</rights><rights>Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-df0ffa62f44d6c0ad3024f748f7848582fa05998c273f1fe30db25dd90bc91d03</citedby><cites>FETCH-LOGICAL-c404t-df0ffa62f44d6c0ad3024f748f7848582fa05998c273f1fe30db25dd90bc91d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S001448272300037X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36706943$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Xuanxuan</creatorcontrib><creatorcontrib>Li, Meiqi</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Sang, Kanru</creatorcontrib><creatorcontrib>Zhang, Yejun</creatorcontrib><creatorcontrib>Li, Wulan</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Wan, Leyu</creatorcontrib><creatorcontrib>Du, Bang</creatorcontrib><creatorcontrib>Qian, Jinheng</creatorcontrib><creatorcontrib>Meng, Fanxi</creatorcontrib><creatorcontrib>Fu, Yanneng</creatorcontrib><creatorcontrib>Dai, Meijuan</creatorcontrib><creatorcontrib>Gao, Guohui</creatorcontrib><creatorcontrib>Ye, Hui</creatorcontrib><title>An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1</title><title>Experimental cell research</title><addtitle>Exp Cell Res</addtitle><description>Thymocyte antigen-1 (THY-1)is a potential target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate RA progression. In this study, we screened an antibody targeting THY-1 (THY-1 Ab) and explored its mechanism in alleviating RA progression. THY-1 Ab was screened from ScFv phage antibody library by phage display technology (PDT). THY-1 Ab–treated collagen induced arthritis (CIA) mice had lower degree of arthritis scores. We explore the mechanism of THY-1 Ab in alleviating RA progression. THY-1 Ab can remarkably inhibit the secretion of pro-inflammatory factors and promote the secretion of anti-inflammatory factors. Further experiments showed that THY1 Ab downregulated the expression of JUNB by the hsa_circ_0094342/miRNA-155–5P/SPI1 axis, inhibited RA angiogenesis and osteoclast differentiation, and relieved RA progression. These findings support that THY-1 Ab is a promising therapeutic antibody for RA treatment.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antigens - immunology</subject><subject>Arthritis, Experimental - metabolism</subject><subject>Arthritis, Experimental - therapy</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Arthritis, Rheumatoid - therapy</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Mice</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Osteoclast differentiation</subject><subject>Osteoclasts - metabolism</subject><subject>Phage display technology</subject><subject>Rheumatoid arthritis</subject><subject>Synovial Membrane - metabolism</subject><subject>THY-1 Ab</subject><subject>Thymocytes - metabolism</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2O1DAQhCMEYoeFJ0BCPnLJ0HY8-UHisFrxJ63EAThbjt1OPErsYDujzbvxcHh2Fo6cWlZ_VaV2FcVrCnsKtH533G94r8KeAav2lFa8gyfFjkIHJeOMPS12AJSXvGXNVfEixiMAtC2tnxdXVd1A3fFqV_y-ccQ6508y2RMSO8-r82nEIBdck1UkpiATDhsxPpAw4jrL5K0mMqQx2GTje_IdJ1Rn-bSRuC5LwBitG4h0g_UDOow25ocmPib0apIxEW2NwYAu2RzsHelzwDplgzEHuEwn23u9kSTDgOnslsZt9mpL-LDMtiV9WTwzcor46nFeFz8_ffxx-6W8-_b56-3NXak48FRqA8bImhnOda1A6goYNw1vTdPy9tAyI-HQda1iTWWowQp0zw5ad9Crjmqorou3F98l-F8rxiRmGxVOk3To1yhY0wBvGnpoMlpdUBV8jAGNWIKdZdgEBXGuTRzFQ23iXJu41JZVbx4D1n5G_U_zt6cMfLgAmM88WQwiKotOobYh_73Q3v434A89IrFy</recordid><startdate>20230301</startdate><enddate>20230301</enddate><creator>Hu, Xuanxuan</creator><creator>Li, Meiqi</creator><creator>Zhang, Yu</creator><creator>Sang, Kanru</creator><creator>Zhang, Yejun</creator><creator>Li, Wulan</creator><creator>Liu, Bo</creator><creator>Wan, Leyu</creator><creator>Du, Bang</creator><creator>Qian, Jinheng</creator><creator>Meng, Fanxi</creator><creator>Fu, Yanneng</creator><creator>Dai, Meijuan</creator><creator>Gao, Guohui</creator><creator>Ye, Hui</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20230301</creationdate><title>An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1</title><author>Hu, Xuanxuan ; Li, Meiqi ; Zhang, Yu ; Sang, Kanru ; Zhang, Yejun ; Li, Wulan ; Liu, Bo ; Wan, Leyu ; Du, Bang ; Qian, Jinheng ; Meng, Fanxi ; Fu, Yanneng ; Dai, Meijuan ; Gao, Guohui ; Ye, Hui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-df0ffa62f44d6c0ad3024f748f7848582fa05998c273f1fe30db25dd90bc91d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antigens - immunology</topic><topic>Arthritis, Experimental - metabolism</topic><topic>Arthritis, Experimental - therapy</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Arthritis, Rheumatoid - therapy</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Mice</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Osteoclast differentiation</topic><topic>Osteoclasts - metabolism</topic><topic>Phage display technology</topic><topic>Rheumatoid arthritis</topic><topic>Synovial Membrane - metabolism</topic><topic>THY-1 Ab</topic><topic>Thymocytes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Xuanxuan</creatorcontrib><creatorcontrib>Li, Meiqi</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Sang, Kanru</creatorcontrib><creatorcontrib>Zhang, Yejun</creatorcontrib><creatorcontrib>Li, Wulan</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Wan, Leyu</creatorcontrib><creatorcontrib>Du, Bang</creatorcontrib><creatorcontrib>Qian, Jinheng</creatorcontrib><creatorcontrib>Meng, Fanxi</creatorcontrib><creatorcontrib>Fu, Yanneng</creatorcontrib><creatorcontrib>Dai, Meijuan</creatorcontrib><creatorcontrib>Gao, Guohui</creatorcontrib><creatorcontrib>Ye, Hui</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><jtitle>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Xuanxuan</au><au>Li, Meiqi</au><au>Zhang, Yu</au><au>Sang, Kanru</au><au>Zhang, Yejun</au><au>Li, Wulan</au><au>Liu, Bo</au><au>Wan, Leyu</au><au>Du, Bang</au><au>Qian, Jinheng</au><au>Meng, Fanxi</au><au>Fu, Yanneng</au><au>Dai, Meijuan</au><au>Gao, Guohui</au><au>Ye, Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1</atitle><jtitle>Experimental cell research</jtitle><addtitle>Exp Cell Res</addtitle><date>2023-03-01</date><risdate>2023</risdate><volume>424</volume><issue>1</issue><spage>113490</spage><epage>113490</epage><pages>113490-113490</pages><artnum>113490</artnum><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>Thymocyte antigen-1 (THY-1)is a potential target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate RA progression. In this study, we screened an antibody targeting THY-1 (THY-1 Ab) and explored its mechanism in alleviating RA progression. THY-1 Ab was screened from ScFv phage antibody library by phage display technology (PDT). THY-1 Ab–treated collagen induced arthritis (CIA) mice had lower degree of arthritis scores. We explore the mechanism of THY-1 Ab in alleviating RA progression. THY-1 Ab can remarkably inhibit the secretion of pro-inflammatory factors and promote the secretion of anti-inflammatory factors. Further experiments showed that THY1 Ab downregulated the expression of JUNB by the hsa_circ_0094342/miRNA-155–5P/SPI1 axis, inhibited RA angiogenesis and osteoclast differentiation, and relieved RA progression. These findings support that THY-1 Ab is a promising therapeutic antibody for RA treatment.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>36706943</pmid><doi>10.1016/j.yexcr.2023.113490</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Angiogenesis Animals Antigens - immunology Arthritis, Experimental - metabolism Arthritis, Experimental - therapy Arthritis, Rheumatoid - metabolism Arthritis, Rheumatoid - therapy Cell Proliferation Cells, Cultured Fibroblasts - metabolism Humans Immunotherapy Mice MicroRNAs - genetics MicroRNAs - metabolism Osteoclast differentiation Osteoclasts - metabolism Phage display technology Rheumatoid arthritis Synovial Membrane - metabolism THY-1 Ab Thymocytes - metabolism |
title | An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1 |
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