Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles
Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets. We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain reperto...
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| Veröffentlicht in: | Journal of autoimmunity 2022-12, Vol.133, p.102907-102907, Article 102907 |
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| container_title | Journal of autoimmunity |
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| creator | Nagafuchi, Yasuo Ota, Mineto Hatano, Hiroaki Inoue, Mariko Kobayashi, Satomi Okubo, Mai Sugimori, Yusuke Nakano, Masahiro Yamada, Saeko Yoshida, Ryochi Tsuchida, Yumi Iwasaki, Yukiko Shoda, Hirofumi Okada, Yukinori Yamamoto, Kazuhiko Ishigaki, Kazuyoshi Okamura, Tomohisa Fujio, Keishi |
| description | Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets.
We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls.
HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling.
This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.
•Risk HLA alleles regulate TRBV gene usage of naive and effector CD4 T cells.•T cell receptor (TCR) public clones accumulate in Th17 cells.•Risk HLA alleles regulate T cell receptor public clones of effector CD4 T cells.•TCR clonal diversity are correlated with TCR signaling transcriptome changes. |
| doi_str_mv | 10.1016/j.jaut.2022.102907 |
| format | Article |
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We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls.
HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling.
This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.
•Risk HLA alleles regulate TRBV gene usage of naive and effector CD4 T cells.•T cell receptor (TCR) public clones accumulate in Th17 cells.•Risk HLA alleles regulate T cell receptor public clones of effector CD4 T cells.•TCR clonal diversity are correlated with TCR signaling transcriptome changes.</description><identifier>ISSN: 0896-8411</identifier><identifier>EISSN: 1095-9157</identifier><identifier>DOI: 10.1016/j.jaut.2022.102907</identifier><identifier>PMID: 36126366</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>HLA ; Immune-mediated disease ; Public clones ; Rheumatoid arthritis ; T cell receptor ; Th17</subject><ispartof>Journal of autoimmunity, 2022-12, Vol.133, p.102907-102907, Article 102907</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-f33ae4758c1c5f737e409b7a252619ddff81528e89413da5274d4b2987095ec23</citedby><cites>FETCH-LOGICAL-c400t-f33ae4758c1c5f737e409b7a252619ddff81528e89413da5274d4b2987095ec23</cites><orcidid>0000-0002-1316-8035</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jaut.2022.102907$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36126366$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagafuchi, Yasuo</creatorcontrib><creatorcontrib>Ota, Mineto</creatorcontrib><creatorcontrib>Hatano, Hiroaki</creatorcontrib><creatorcontrib>Inoue, Mariko</creatorcontrib><creatorcontrib>Kobayashi, Satomi</creatorcontrib><creatorcontrib>Okubo, Mai</creatorcontrib><creatorcontrib>Sugimori, Yusuke</creatorcontrib><creatorcontrib>Nakano, Masahiro</creatorcontrib><creatorcontrib>Yamada, Saeko</creatorcontrib><creatorcontrib>Yoshida, Ryochi</creatorcontrib><creatorcontrib>Tsuchida, Yumi</creatorcontrib><creatorcontrib>Iwasaki, Yukiko</creatorcontrib><creatorcontrib>Shoda, Hirofumi</creatorcontrib><creatorcontrib>Okada, Yukinori</creatorcontrib><creatorcontrib>Yamamoto, Kazuhiko</creatorcontrib><creatorcontrib>Ishigaki, Kazuyoshi</creatorcontrib><creatorcontrib>Okamura, Tomohisa</creatorcontrib><creatorcontrib>Fujio, Keishi</creatorcontrib><title>Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles</title><title>Journal of autoimmunity</title><addtitle>J Autoimmun</addtitle><description>Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets.
We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls.
HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling.
This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.
•Risk HLA alleles regulate TRBV gene usage of naive and effector CD4 T cells.•T cell receptor (TCR) public clones accumulate in Th17 cells.•Risk HLA alleles regulate T cell receptor public clones of effector CD4 T cells.•TCR clonal diversity are correlated with TCR signaling transcriptome changes.</description><subject>HLA</subject><subject>Immune-mediated disease</subject><subject>Public clones</subject><subject>Rheumatoid arthritis</subject><subject>T cell receptor</subject><subject>Th17</subject><issn>0896-8411</issn><issn>1095-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kM1LxDAQxYMoun78Ax4kRy9dM2nTtOBF1k9Y8KLnkE0mmLXbrEkq-N_bsurR0zDDe495P0LOgc2BQX21nq_1kOeccT4eeMvkHpkBa0XRgpD7ZMaati6aCuCIHKe0ZgxACHFIjsoaeF3W9Yy4RehzDB0NjvbafyLVvaXoHJocIl3cVvSFGuw6GtHgdrpF3GLMwUdMdPVF4xsOGz3uttAxv0WffSqiT-_0cXlDdddhh-mUHDjdJTz7mSfk9f7uZfFYLJ8fnhY3y8JUjOXClaXGSorGgBFOlhIr1q6k5oLX0FrrXAOCN9i0FZRWCy4rW61428ixNRpenpDLXe42ho8BU1Ybn6b3dY9hSIpLqAUXksMo5TupiSGliE5to9_o-KWAqYmvWquJr5r4qh3f0XTxkz-sNmj_LL9AR8H1ToBjy0-PUSXjsTdoR14mKxv8f_nfuxeLUw</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Nagafuchi, Yasuo</creator><creator>Ota, Mineto</creator><creator>Hatano, Hiroaki</creator><creator>Inoue, Mariko</creator><creator>Kobayashi, Satomi</creator><creator>Okubo, Mai</creator><creator>Sugimori, Yusuke</creator><creator>Nakano, Masahiro</creator><creator>Yamada, Saeko</creator><creator>Yoshida, Ryochi</creator><creator>Tsuchida, Yumi</creator><creator>Iwasaki, Yukiko</creator><creator>Shoda, Hirofumi</creator><creator>Okada, Yukinori</creator><creator>Yamamoto, Kazuhiko</creator><creator>Ishigaki, Kazuyoshi</creator><creator>Okamura, Tomohisa</creator><creator>Fujio, Keishi</creator><general>Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1316-8035</orcidid></search><sort><creationdate>202212</creationdate><title>Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles</title><author>Nagafuchi, Yasuo ; Ota, Mineto ; Hatano, Hiroaki ; Inoue, Mariko ; Kobayashi, Satomi ; Okubo, Mai ; Sugimori, Yusuke ; Nakano, Masahiro ; Yamada, Saeko ; Yoshida, Ryochi ; Tsuchida, Yumi ; Iwasaki, Yukiko ; Shoda, Hirofumi ; Okada, Yukinori ; Yamamoto, Kazuhiko ; Ishigaki, Kazuyoshi ; Okamura, Tomohisa ; Fujio, Keishi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-f33ae4758c1c5f737e409b7a252619ddff81528e89413da5274d4b2987095ec23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>HLA</topic><topic>Immune-mediated disease</topic><topic>Public clones</topic><topic>Rheumatoid arthritis</topic><topic>T cell receptor</topic><topic>Th17</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagafuchi, Yasuo</creatorcontrib><creatorcontrib>Ota, Mineto</creatorcontrib><creatorcontrib>Hatano, Hiroaki</creatorcontrib><creatorcontrib>Inoue, Mariko</creatorcontrib><creatorcontrib>Kobayashi, Satomi</creatorcontrib><creatorcontrib>Okubo, Mai</creatorcontrib><creatorcontrib>Sugimori, Yusuke</creatorcontrib><creatorcontrib>Nakano, Masahiro</creatorcontrib><creatorcontrib>Yamada, Saeko</creatorcontrib><creatorcontrib>Yoshida, Ryochi</creatorcontrib><creatorcontrib>Tsuchida, Yumi</creatorcontrib><creatorcontrib>Iwasaki, Yukiko</creatorcontrib><creatorcontrib>Shoda, Hirofumi</creatorcontrib><creatorcontrib>Okada, Yukinori</creatorcontrib><creatorcontrib>Yamamoto, Kazuhiko</creatorcontrib><creatorcontrib>Ishigaki, Kazuyoshi</creatorcontrib><creatorcontrib>Okamura, Tomohisa</creatorcontrib><creatorcontrib>Fujio, Keishi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of autoimmunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagafuchi, Yasuo</au><au>Ota, Mineto</au><au>Hatano, Hiroaki</au><au>Inoue, Mariko</au><au>Kobayashi, Satomi</au><au>Okubo, Mai</au><au>Sugimori, Yusuke</au><au>Nakano, Masahiro</au><au>Yamada, Saeko</au><au>Yoshida, Ryochi</au><au>Tsuchida, Yumi</au><au>Iwasaki, Yukiko</au><au>Shoda, Hirofumi</au><au>Okada, Yukinori</au><au>Yamamoto, Kazuhiko</au><au>Ishigaki, Kazuyoshi</au><au>Okamura, Tomohisa</au><au>Fujio, Keishi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles</atitle><jtitle>Journal of autoimmunity</jtitle><addtitle>J Autoimmun</addtitle><date>2022-12</date><risdate>2022</risdate><volume>133</volume><spage>102907</spage><epage>102907</epage><pages>102907-102907</pages><artnum>102907</artnum><issn>0896-8411</issn><eissn>1095-9157</eissn><abstract>Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets.
We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls.
HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling.
This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients.
•Risk HLA alleles regulate TRBV gene usage of naive and effector CD4 T cells.•T cell receptor (TCR) public clones accumulate in Th17 cells.•Risk HLA alleles regulate T cell receptor public clones of effector CD4 T cells.•TCR clonal diversity are correlated with TCR signaling transcriptome changes.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>36126366</pmid><doi>10.1016/j.jaut.2022.102907</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-1316-8035</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | HLA Immune-mediated disease Public clones Rheumatoid arthritis T cell receptor Th17 |
| title | Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles |
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