Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles

Yasuo Nagafuchi; Mineto Ota; Hiroaki Hatano; Mariko Inoue; Satomi Kobayashi; Mai Okubo; Yusuke Sugimori; Masahiro Nakano; Saeko Yamada; Ryochi Yoshida; Yumi Tsuchida; Yukiko Iwasaki; Hirofumi Shoda; Yukinori Okada; Kazuhiko Yamamoto; Kazuyoshi Ishigaki; Tomohisa Okamura; Keishi Fujio

doi:10.1016/j.jaut.2022.102907

Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles

Yasuo Nagafuchi, Mineto Ota, Hiroaki Hatano, Mariko Inoue, Satomi Kobayashi, Mai Okubo, Yusuke Sugimori, Masahiro Nakano, Saeko Yamada, Ryochi Yoshida, Yumi Tsuchida, Yukiko Iwasaki, Hirofumi Shoda, Yukinori Okada, Kazuhiko Yamamoto, Kazuyoshi Ishigaki, Tomohisa Okamura, Keishi Fujio

研究成果: Article › 査読

2 被引用数 (Scopus)

抄録

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

本文言語	English
論文番号	102907
ジャーナル	Journal of Autoimmunity
巻	133
DOI	https://doi.org/10.1016/j.jaut.2022.102907
出版ステータス	Published - 2022 12月
外部発表	はい

ASJC Scopus subject areas

免疫アレルギー学
免疫学

UN SDG

この成果は、次の持続可能な開発目標に貢献しています

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10.1016/j.jaut.2022.102907

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引用スタイル

Nagafuchi, Y., Ota, M., Hatano, H., Inoue, M., Kobayashi, S., Okubo, M., Sugimori, Y., Nakano, M., Yamada, S., Yoshida, R., Tsuchida, Y., Iwasaki, Y., Shoda, H., Okada, Y., Yamamoto, K., Ishigaki, K., Okamura, T., & Fujio, K. (2022). Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles. Journal of Autoimmunity, 133, 記事 102907. https://doi.org/10.1016/j.jaut.2022.102907

Nagafuchi, Y, Ota, M, Hatano, H, Inoue, M, Kobayashi, S, Okubo, M, Sugimori, Y, Nakano, M, Yamada, S, Yoshida, R, Tsuchida, Y, Iwasaki, Y, Shoda, H, Okada, Y, Yamamoto, K, Ishigaki, K, Okamura, T & Fujio, K 2022, 'Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles', Journal of Autoimmunity, vol. 133, 102907. https://doi.org/10.1016/j.jaut.2022.102907

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title = "Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles",

abstract = "Objective: 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. Methods: 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. Results: 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. Conclusion: 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.",

keywords = "HLA, Immune-mediated disease, Public clones, Rheumatoid arthritis, T cell receptor, Th17",

author = "Yasuo Nagafuchi and Mineto Ota and Hiroaki Hatano and Mariko Inoue and Satomi Kobayashi and Mai Okubo and Yusuke Sugimori and Masahiro Nakano and Saeko Yamada and Ryochi Yoshida and Yumi Tsuchida and Yukiko Iwasaki and Hirofumi Shoda and Yukinori Okada and Kazuhiko Yamamoto and Kazuyoshi Ishigaki and Tomohisa Okamura and Keishi Fujio",

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year = "2022",

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doi = "10.1016/j.jaut.2022.102907",

language = "English",

volume = "133",

journal = "Journal of Autoimmunity",

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T1 - Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles

AU - Nagafuchi, Yasuo

AU - Ota, Mineto

AU - Hatano, Hiroaki

AU - Inoue, Mariko

AU - Kobayashi, Satomi

AU - Okubo, Mai

AU - Sugimori, Yusuke

AU - Nakano, Masahiro

AU - Yamada, Saeko

AU - Yoshida, Ryochi

AU - Tsuchida, Yumi

AU - Iwasaki, Yukiko

AU - Shoda, Hirofumi

AU - Okada, Yukinori

AU - Yamamoto, Kazuhiko

AU - Ishigaki, Kazuyoshi

AU - Okamura, Tomohisa

AU - Fujio, Keishi

PY - 2022/12

Y1 - 2022/12

N2 - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

AB - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

KW - HLA

KW - Immune-mediated disease

KW - Public clones

KW - Rheumatoid arthritis

KW - T cell receptor

KW - Th17

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Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles

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ASJC Scopus subject areas

UN SDG

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