GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T h 1/T h 17 and regulatory T cells
Rheumatoid arthritis (RA) is an autoimmune disease associated with synovial hyperplasia and bone and cartilage destruction. T cells, notably T helper (T )-1 and T 17 cells, play a critical role in the pathologic process of RA. However, it remains unclear how T 1 and T 17 cells are regulated during R...
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Veröffentlicht in: | The FASEB journal 2019-07, Vol.33 (7), p.8375-8385 |
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creator | Fu, Yanxia Liu, Sihan Wang, Yinyin Ren, Fangli Fan, Xuanzi Liang, Jiao Liu, Chunxiao Li, Jun Ju, Yanfang Chang, Zhijie |
description | Rheumatoid arthritis (RA) is an autoimmune disease associated with synovial hyperplasia and bone and cartilage destruction. T cells, notably T helper (T
)-1 and T
17 cells, play a critical role in the pathologic process of RA. However, it remains unclear how T
1 and T
17 cells are regulated during RA. In this study, we report that the small ubiquitin-like protein X-linked gene in the G6PD cluster at Xq28 (GdX) regulates the balance of T
17 and regulatory T (T
) cells during collagen-induced arthritis (CIA). We discovered that the splenocytes of GdX-knockout (KO) mice were insensitive to T-cell stimulants. Correspondingly, GdX-KO mice showed alleviative T
1-mediated delayed-type hypersensitivity and were resistant to CIA compared with wild-type mice. GdX-KO mice showed fewer swollen paws, lower serum proinflammatory cytokine and anti-collagen IgG levels, and decreased synovial hyperplasia. Mechanistically, we observed that deletion of GdX decreased the transcription of proinflammatory cytokines and impaired the T
1 and T
17 differentiation but increased the T
cell proliferation. Consistently, deletion of GdX decreased the transcription level of T-cell-specific T-box transcription factor and RAR-related orphan receptor-γ transcription factor but increased that of forkhead box P3 after being challenged with type-II collagen. These findings suggested that GdX functions as an important regulator of T
1 or T
17 and T
cell balance during the inflammatory responses. Therefore, GdX may be a potential target for the therapy of RA.-Fu, Y., Liu, S., Wang, Y., Ren, F., Fan, X., Liang, J., Liu, C., Li, J., Ju, Y., Chang, Z. GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T
1/T
17 and regulatory T cells. |
doi_str_mv | 10.1096/fj.201802217RR |
format | Article |
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)-1 and T
17 cells, play a critical role in the pathologic process of RA. However, it remains unclear how T
1 and T
17 cells are regulated during RA. In this study, we report that the small ubiquitin-like protein X-linked gene in the G6PD cluster at Xq28 (GdX) regulates the balance of T
17 and regulatory T (T
) cells during collagen-induced arthritis (CIA). We discovered that the splenocytes of GdX-knockout (KO) mice were insensitive to T-cell stimulants. Correspondingly, GdX-KO mice showed alleviative T
1-mediated delayed-type hypersensitivity and were resistant to CIA compared with wild-type mice. GdX-KO mice showed fewer swollen paws, lower serum proinflammatory cytokine and anti-collagen IgG levels, and decreased synovial hyperplasia. Mechanistically, we observed that deletion of GdX decreased the transcription of proinflammatory cytokines and impaired the T
1 and T
17 differentiation but increased the T
cell proliferation. Consistently, deletion of GdX decreased the transcription level of T-cell-specific T-box transcription factor and RAR-related orphan receptor-γ transcription factor but increased that of forkhead box P3 after being challenged with type-II collagen. These findings suggested that GdX functions as an important regulator of T
1 or T
17 and T
cell balance during the inflammatory responses. Therefore, GdX may be a potential target for the therapy of RA.-Fu, Y., Liu, S., Wang, Y., Ren, F., Fan, X., Liang, J., Liu, C., Li, J., Ju, Y., Chang, Z. GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T
1/T
17 and regulatory T cells.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.201802217RR</identifier><identifier>PMID: 31002527</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Arthritis, Experimental - enzymology ; Arthritis, Experimental - genetics ; Arthritis, Experimental - pathology ; Cytokines - genetics ; Cytokines - metabolism ; Male ; Mice ; Mice, Knockout ; T-Lymphocytes, Regulatory - enzymology ; Th1 Cells - enzymology ; Th1 Cells - pathology ; Th17 Cells - enzymology ; Th17 Cells - pathology ; Transcription, Genetic ; Ubiquitins - deficiency ; Ubiquitins - metabolism</subject><ispartof>The FASEB journal, 2019-07, Vol.33 (7), p.8375-8385</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1077-47e0523fdf23fa72bed1ef3a8fc2338385fe773b5030ac9dad49ac6e869ca0703</citedby><cites>FETCH-LOGICAL-c1077-47e0523fdf23fa72bed1ef3a8fc2338385fe773b5030ac9dad49ac6e869ca0703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31002527$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fu, Yanxia</creatorcontrib><creatorcontrib>Liu, Sihan</creatorcontrib><creatorcontrib>Wang, Yinyin</creatorcontrib><creatorcontrib>Ren, Fangli</creatorcontrib><creatorcontrib>Fan, Xuanzi</creatorcontrib><creatorcontrib>Liang, Jiao</creatorcontrib><creatorcontrib>Liu, Chunxiao</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Ju, Yanfang</creatorcontrib><creatorcontrib>Chang, Zhijie</creatorcontrib><title>GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T h 1/T h 17 and regulatory T cells</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>Rheumatoid arthritis (RA) is an autoimmune disease associated with synovial hyperplasia and bone and cartilage destruction. T cells, notably T helper (T
)-1 and T
17 cells, play a critical role in the pathologic process of RA. However, it remains unclear how T
1 and T
17 cells are regulated during RA. In this study, we report that the small ubiquitin-like protein X-linked gene in the G6PD cluster at Xq28 (GdX) regulates the balance of T
17 and regulatory T (T
) cells during collagen-induced arthritis (CIA). We discovered that the splenocytes of GdX-knockout (KO) mice were insensitive to T-cell stimulants. Correspondingly, GdX-KO mice showed alleviative T
1-mediated delayed-type hypersensitivity and were resistant to CIA compared with wild-type mice. GdX-KO mice showed fewer swollen paws, lower serum proinflammatory cytokine and anti-collagen IgG levels, and decreased synovial hyperplasia. Mechanistically, we observed that deletion of GdX decreased the transcription of proinflammatory cytokines and impaired the T
1 and T
17 differentiation but increased the T
cell proliferation. Consistently, deletion of GdX decreased the transcription level of T-cell-specific T-box transcription factor and RAR-related orphan receptor-γ transcription factor but increased that of forkhead box P3 after being challenged with type-II collagen. These findings suggested that GdX functions as an important regulator of T
1 or T
17 and T
cell balance during the inflammatory responses. Therefore, GdX may be a potential target for the therapy of RA.-Fu, Y., Liu, S., Wang, Y., Ren, F., Fan, X., Liang, J., Liu, C., Li, J., Ju, Y., Chang, Z. GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T
1/T
17 and regulatory T cells.</description><subject>Animals</subject><subject>Arthritis, Experimental - enzymology</subject><subject>Arthritis, Experimental - genetics</subject><subject>Arthritis, Experimental - pathology</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>T-Lymphocytes, Regulatory - enzymology</subject><subject>Th1 Cells - enzymology</subject><subject>Th1 Cells - pathology</subject><subject>Th17 Cells - enzymology</subject><subject>Th17 Cells - pathology</subject><subject>Transcription, Genetic</subject><subject>Ubiquitins - deficiency</subject><subject>Ubiquitins - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1PwjAcxhujEUSvHk2_wODflrXdEY2iCYkJgcTb0vUFBmNd2u1A4od3iBovz3N4Xg4_hO4JjAlkfOJ2YwpEAqVELJcXaEhSBgmXHC7REGRGE86ZHKCbGHcAQIDwazRgBICmVAzR59x8TNaPi-ks2dde733X4kOpLQ42lrHF2leV2tg6KWvTaWuwCu02lG0ZcXHEhapUrct6g9utxY1vukq1pa-xd3iFt5hMvlVgVZv-cXOKfTj2mbZVFW_RlVNVtHc_PkLrl-fV02uyeJ-_Pc0WiSYgRDIVFlLKnHG9KEELa4h1TEmnKWOSydRZIViRAgOlM6PMNFOaW8kzrUAAG6Hx-VcHH2OwLm9CeVDhmBPITxhzt8v_YewHD-dB0xUHa_7qv9zYF8zPbes</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Fu, Yanxia</creator><creator>Liu, Sihan</creator><creator>Wang, Yinyin</creator><creator>Ren, Fangli</creator><creator>Fan, Xuanzi</creator><creator>Liang, Jiao</creator><creator>Liu, Chunxiao</creator><creator>Li, Jun</creator><creator>Ju, Yanfang</creator><creator>Chang, Zhijie</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201907</creationdate><title>GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T h 1/T h 17 and regulatory T cells</title><author>Fu, Yanxia ; Liu, Sihan ; Wang, Yinyin ; Ren, Fangli ; Fan, Xuanzi ; Liang, Jiao ; Liu, Chunxiao ; Li, Jun ; Ju, Yanfang ; Chang, Zhijie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1077-47e0523fdf23fa72bed1ef3a8fc2338385fe773b5030ac9dad49ac6e869ca0703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Arthritis, Experimental - enzymology</topic><topic>Arthritis, Experimental - genetics</topic><topic>Arthritis, Experimental - pathology</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>T-Lymphocytes, Regulatory - enzymology</topic><topic>Th1 Cells - enzymology</topic><topic>Th1 Cells - pathology</topic><topic>Th17 Cells - enzymology</topic><topic>Th17 Cells - pathology</topic><topic>Transcription, Genetic</topic><topic>Ubiquitins - deficiency</topic><topic>Ubiquitins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fu, Yanxia</creatorcontrib><creatorcontrib>Liu, Sihan</creatorcontrib><creatorcontrib>Wang, Yinyin</creatorcontrib><creatorcontrib>Ren, Fangli</creatorcontrib><creatorcontrib>Fan, Xuanzi</creatorcontrib><creatorcontrib>Liang, Jiao</creatorcontrib><creatorcontrib>Liu, Chunxiao</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Ju, Yanfang</creatorcontrib><creatorcontrib>Chang, Zhijie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fu, Yanxia</au><au>Liu, Sihan</au><au>Wang, Yinyin</au><au>Ren, Fangli</au><au>Fan, Xuanzi</au><au>Liang, Jiao</au><au>Liu, Chunxiao</au><au>Li, Jun</au><au>Ju, Yanfang</au><au>Chang, Zhijie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T h 1/T h 17 and regulatory T cells</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2019-07</date><risdate>2019</risdate><volume>33</volume><issue>7</issue><spage>8375</spage><epage>8385</epage><pages>8375-8385</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>Rheumatoid arthritis (RA) is an autoimmune disease associated with synovial hyperplasia and bone and cartilage destruction. T cells, notably T helper (T
)-1 and T
17 cells, play a critical role in the pathologic process of RA. However, it remains unclear how T
1 and T
17 cells are regulated during RA. In this study, we report that the small ubiquitin-like protein X-linked gene in the G6PD cluster at Xq28 (GdX) regulates the balance of T
17 and regulatory T (T
) cells during collagen-induced arthritis (CIA). We discovered that the splenocytes of GdX-knockout (KO) mice were insensitive to T-cell stimulants. Correspondingly, GdX-KO mice showed alleviative T
1-mediated delayed-type hypersensitivity and were resistant to CIA compared with wild-type mice. GdX-KO mice showed fewer swollen paws, lower serum proinflammatory cytokine and anti-collagen IgG levels, and decreased synovial hyperplasia. Mechanistically, we observed that deletion of GdX decreased the transcription of proinflammatory cytokines and impaired the T
1 and T
17 differentiation but increased the T
cell proliferation. Consistently, deletion of GdX decreased the transcription level of T-cell-specific T-box transcription factor and RAR-related orphan receptor-γ transcription factor but increased that of forkhead box P3 after being challenged with type-II collagen. These findings suggested that GdX functions as an important regulator of T
1 or T
17 and T
cell balance during the inflammatory responses. Therefore, GdX may be a potential target for the therapy of RA.-Fu, Y., Liu, S., Wang, Y., Ren, F., Fan, X., Liang, J., Liu, C., Li, J., Ju, Y., Chang, Z. GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T
1/T
17 and regulatory T cells.</abstract><cop>United States</cop><pmid>31002527</pmid><doi>10.1096/fj.201802217RR</doi><tpages>11</tpages></addata></record> |
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subjects | Animals Arthritis, Experimental - enzymology Arthritis, Experimental - genetics Arthritis, Experimental - pathology Cytokines - genetics Cytokines - metabolism Male Mice Mice, Knockout T-Lymphocytes, Regulatory - enzymology Th1 Cells - enzymology Th1 Cells - pathology Th17 Cells - enzymology Th17 Cells - pathology Transcription, Genetic Ubiquitins - deficiency Ubiquitins - metabolism |
title | GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T h 1/T h 17 and regulatory T cells |
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