Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity.
Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity.
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DOI：
10.1038/s41588-023-01375-1
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发表时间：
2023-05
期刊：
影响因子：
30.8
通讯作者：
Fukunaga, Koichi
中科院分区：
文献类型：
--
作者：
Edahiro, Ryuya;Shirai, Yuya;Takeshima, Yusuke;Sakakibara, Shuhei;Yamaguchi, Yuta;Murakami, Teruaki;Morita, Takayoshi;Kato, Yasuhiro;Liu, Yu-Chen;Motooka, Daisuke;Naito, Yoko;Takuwa, Ayako;Sugihara, Fuminori;Tanaka, Kentaro;Wing, James B.;Sonehara, Kyuto;Tomofuji, Yoshihiko;Namkoong, Ho;Tanaka, Hiromu;Lee, Ho;Fukunaga, Koichi;Hirata, Haruhiko;Takeda, Yoshito;Okuzaki, Daisuke;Kumanogoh, Atsushi;Okada, Yukinori;Wang, Qingbo S.;Edahiro, Ryuya;Namkoong, Ho;Hasegawa, Takanori;Shirai, Yuya;Sonehara, Kyuto;Tanaka, Hiromu;Lee, Ho;Saiki, Ryunosuke;Hyugaji, Takayoshi;Shimizu, Eigo;Katayama, Kotoe;Kanai, Masahiro;Naito, Tatsuhiko;Sasa, Noah;Yamamoto, Kenichi;Kato, Yasuhiro;Morita, Takayoshi;Takahashi, Kazuhisa;Harada, Norihiro;Naito, Toshio;Hiki, Makoto;Matsushita, Yasushi;Takagi, Haruhi;Ichikawa, Masako;Nakamura, Ai;Harada, Sonoko;Sandhu, Yuuki;Kabata, Hiroki;Masaki, Katsunori;Kamata, Hirofumi;Ikemura, Shinnosuke;Chubachi, Shotaro;Okamori, Satoshi;Terai, Hideki;Morita, Atsuho;Asakura, Takanori;Sasaki, Junichi;Morisaki, Hiroshi;Uwamino, Yoshifumi;Nanki, Kosaku;Uchida, Sho;Uno, Shunsuke;Nishimura, Tomoyasu;Ishiguro, Takashi;Isono, Taisuke;Shibata, Shun;Matsui, Yuma;Hosoda, Chiaki;Takano, Kenji;Nishida, Takashi;Kobayashi, Yoichi;Takaku, Yotaro;Takayanagi, Noboru;Ueda, Soichiro;Tada, Ai;Miyawaki, Masayoshi;Yamamoto, Masaomi;Yoshida, Eriko;Hayashi, Reina;Nagasaka, Tomoki;Arai, Sawako;Kaneko, Yutaro;Sasaki, Kana;Tagaya, Etsuko;Kawana, Masatoshi;Arimura, Ken;Takahashi, Kunihiko;Anzai, Tatsuhiko;Ito, Satoshi;Endo, Akifumi;Uchimura, Yuji;Miyazaki, Yasunari;Honda, Takayuki;Tateishi, Tomoya;Tohda, Shuji;Ichimura, Naoya;Sonobe, Kazunari;Sassa, Chihiro Tani;Nakajima, Jun;Nakano, Yasushi;Nakajima, Yukiko;Anan, Ryusuke;Arai, Ryosuke;Kurihara, Yuko;Harada, Yuko;Nishio, Kazumi;Ueda, Tetsuya;Azuma, Masanori;Saito, Ryuichi;Sado, Toshikatsu;Miyazaki, Yoshimune;Sato, Ryuichi;Haruta, Yuki;Nagasaki, Tadao;Yasui, Yoshinori;Hasegawa, Yoshinori;Mutoh, Yoshikazu;Kimura, Tomoki;Sato, Tomonori;Takei, Reoto;Hagimoto, Satoshi;Noguchi, Yoichiro;Yamano, Yasuhiko;Sasano, Hajime;Ota, Sho;Nakamori, Yasushi;Yoshiya, Kazuhisa;Saito, Fukuki;Yoshihara, Tomoyuki;Wada, Daiki;Iwamura, Hiromu;Kanayama, Syuji;Maruyama, Shuhei;Yoshiyama, Takashi;Ohta, Ken;Kokuto, Hiroyuki;Ogata, Hideo;Tanaka, Yoshiaki;Arakawa, Kenichi;Shimoda, Masafumi;Osawa, Takeshi;Tateno, Hiroki;Hase, Isano;Yoshida, Shuichi;Suzuki, Shoji;Kawada, Miki;Horinouchi, Hirohisa;Saito, Fumitake;Mitamura, Keiko;Hagihara, Masao;Ochi, Junichi;Uchida, Tomoyuki;Baba, Rie;Arai, Daisuke;Ogura, Takayuki;Takahashi, Hidenori;Hagiwara, Shigehiro;Nagao, Genta;Konishi, Shunichiro;Nakachi, Ichiro;Murakami, Koji;Yamada, Mitsuhiro;Sugiura, Hisatoshi;Sano, Hirohito;Matsumoto, Shuichiro;Kimura, Nozomu;Ono, Yoshinao;Baba, Hiroaki;Suzuki, Yusuke;Nakayama, Sohei;Masuzawa, Keita;Namba, Shinichi;Shiroyama, Takayuki;Noda, Yoshimi;Niitsu, Takayuki;Adachi, Yuichi;Enomoto, Takatoshi;Amiya, Saori;Hara, Reina;Yamaguchi, Yuta;Murakami, Teruaki;Kuge, Tomoki;Matsumoto, Kinnosuke;Yamamoto, Yuji;Yamamoto, Makoto;Yoneda, Midori;Tomono, Kazunori;Kato, Kazuto;Hirata, Haruhiko;Takeda, Yoshito;Koh, Hidefumi;Manabe, Tadashi;Funatsu, Yohei;Ito, Fumimaro;Fukui, Takahiro;Shinozuka, Keisuke;Kohashi, Sumiko;Miyazaki, Masatoshi;Shoko, Tomohisa;Kojima, Mitsuaki;Adachi, Tomohiro;Ishikawa, Motonao;Takahashi, Kenichiro;Inoue, Takashi;Hirano, Toshiyuki;Kobayashi, Keigo;Takaoka, Hatsuyo;Watanabe, Kazuyoshi;Miyazawa, Naoki;Kimura, Yasuhiro;Sado, Reiko;Sugimoto, Hideyasu;Kamiya, Akane;Kuwahara, Naota;Fujiwara, Akiko;Matsunaga, Tomohiro;Sato, Yoko;Okada, Takenori;Hirai, Yoshihiro;Kawashima, Hidetoshi;Narita, Atsuya;Niwa, Kazuki;Sekikawa, Yoshiyuki;Nishi, Koichi;Nishitsuji, Masaru;Tani, Mayuko;Suzuki, Junya;Nakatsumi, Hiroki;Ogura, Takashi;Kitamura, Hideya;Hagiwara, Eri;Murohashi, Kota;Okabayashi, Hiroko;Mochimaru, Takao;Nukaga, Shigenari;Satomi, Ryosuke;Oyamada, Yoshitaka;Mori, Nobuaki;Baba, Tomoya;Fukui, Yasutaka;Odate, Mitsuru;Mashimo, Shuko;Makino, Yasushi;Yagi, Kazuma;Hashiguchi, Mizuha;Kagyo, Junko;Shiomi, Tetsuya;Fuke, Satoshi;Saito, Hiroshi;Tsuchida, Tomoya;Fujitani, Shigeki;Takita, Mumon;Morikawa, Daiki;Yoshida, Toru;Izumo, Takehiro;Inomata, Minoru;Kuse, Naoyuki;Awano, Nobuyasu;Tone, Mari;Ito, Akihiro;Nakamura, Yoshihiko;Hoshino, Kota;Maruyama, Junichi;Ishikura, Hiroyasu;Takata, Tohru;Odani, Toshio;Amishima, Masaru;Hattori, Takeshi;Shichinohe, Yasuo;Kagaya, Takashi;Kita, Toshiyuki;Ohta, Kazuhide;Sakagami, Satoru;Koshida, Kiyoshi;Hayashi, Kentaro;Shimizu, Tetsuo;Kozu, Yutaka;Hiranuma, Hisato;Gon, Yasuhiro;Izumi, Namiki;Nagata, Kaoru;Ueda, Ken;Taki, Reiko;Hanada, Satoko;Kawamura, Kodai;Ichikado, Kazuya;Nishiyama, Kenta;Muranaka, Hiroyuki;Nakamura, Kazunori;Hashimoto, Naozumi;Wakahara, Keiko;Koji, Sakamoto;Omote, Norihito;Ando, Akira;Kodama, Nobuhiro;Kaneyama, Yasunari;Maeda, Shunsuke;Kuraki, Takashige;Matsumoto, Takemasa;Yokote, Koutaro;Nakada, Taka-Aki;Abe, Ryuzo;Oshima, Taku;Shimada, Tadanaga;Harada, Masahiro;Takahashi, Takeshi;Ono, Hiroshi;Sakurai, Toshihiro;Shibusawa, Takayuki;Kimizuka, Yoshifumi;Kawana, Akihiko;Sano, Tomoya;Watanabe, Chie;Suematsu, Ryohei;Sageshima, Hisako;Yoshifuji, Ayumi;Ito, Kazuto;Takahashi, Saeko;Ishioka, Kota;Nakamura, Morio;Masuda, Makoto;Wakabayashi, Aya;Watanabe, Hiroki;Ueda, Suguru;Nishikawa, Masanori;Chihara, Yusuke;Takeuchi, Mayumi;Onoi, Keisuke;Shinozuka, Jun;Sueyoshi, Atsushi;Nagasaki, Yoji;Okamoto, Masaki;Ishihara, Sayoko;Shimo, Masatoshi;Tokunaga, Yoshihisa;Kusaka, Yu;Ohba, Takehiko;Isogai, Susumu;Ogawa, Aki;Inoue, Takuya;Fukuyama, Satoru;Eriguchi, Yoshihiro;Yonekawa, Akiko;Kan-o, Keiko;Matsumoto, Koichiro;Kanaoka, Kensuke;Ihara, Shoichi;Komuta, Kiyoshi;Inoue, Yoshiaki;Chiba, Shigeru;Yamagata, Kunihiro;Hiramatsu, Yuji;Kai, Hirayasu;Asano, Koichiro;Oguma, Tsuyoshi;Ito, Yoko;Hashimoto, Satoru;Yamasaki, Masaki;Kasamatsu, Yu;Komase, Yuko;Hida, Naoya;Tsuburai, Takahiro;Oyama, Baku;Takada, Minoru;Kanda, Hidenori;Kitagawa, Yuichiro;Fukuta, Tetsuya;Miyake, Takahito;Yoshida, Shozo;Ogura, Shinji;Abe, Shinji;Kono, Yuta;Togashi, Yuki;Takoi, Hiroyuki;Kikuchi, Ryota;Ogawa, Shinichi;Ogata, Tomouki;Ishihara, Shoichiro;Kanehiro, Arihiko;Ozaki, Shinji;Fuchimoto, Yasuko;Wada, Sae;Fujimoto, Nobukazu;Nishiyama, Kei;Terashima, Mariko;Beppu, Satoru;Yoshida, Kosuke;Narumoto, Osamu;Nagai, Hideaki;Ooshima, Nobuharu;Motegi, Mitsuru;Umeda, Akira;Miyagawa, Kazuya;Shimada, Hisato;Endo, Mayu;Ohira, Yoshiyuki;Watanabe, Masafumi;Inoue, Sumito;Igarashi, Akira;Sato, Masamichi;Sagara, Hironori;Tanaka, Akihiko;Ohta, Shin;Kimura, Tomoyuki;Shibata, Yoko;Tanino, Yoshinori;Nikaido, Takefumi;Minemura, Hiroyuki;Sato, Yuki;Yamada, Yuichiro;Hashino, Takuya;Shinoki, Masato;Iwagoe, Hajime;Takahashi, Hiroshi;Fujii, Kazuhiko;Kishi, Hiroto;Kanai, Masayuki;Imamura, Tomonori;Yamashita, Tatsuya;Yatomi, Masakiyo;Maeno, Toshitaka;Hayashi, Shinichi;Takahashi, Mai;Kuramochi, Mizuki;Kamimaki, Isamu;Tominaga, Yoshiteru;Ishii, Tomoo;Utsugi, Mitsuyoshi;Ono, Akihiro;Tanaka, Toru;Kashiwada, Takeru;Fujita, Kazue;Saito, Yoshinobu;Seike, Masahiro;Watanabe, Hiroko;Matsuse, Hiroto;Kodaka, Norio;Nakano, Chihiro;Oshio, Takeshi;Hirouchi, Takatomo;Makino, Shohei;Egi, Moritoki;Omae, Yosuke;Nannya, Yasuhito;Ueno, Takafumi;Takano, Tomomi;Katayama, Kazuhiko;Ai, Masumi;Kumanogoh, Atsushi;Sato, Toshiro;Hasegawa, Naoki;Tokunaga, Katsushi;Ishii, Makoto;Koike, Ryuji;Kitagawa, Yuko;Kimura, Akinori;Imoto, Seiya;Miyano, Satoru;Ogawa, Seishi;Kanai, Takanori;Fukunaga, Koichi
严重急性呼吸综合征冠状病毒2感染中免疫反应功能失调的机制尚不清楚。我们分析了73名2019冠状病毒病（COVID-19）患者和75名具有宿主遗传数据的日本血统健康对照的bb895,000个外周血单个核细胞的单细胞转录组和T细胞和B细胞受体（BCR）。COVID-19患者的非经典单核细胞（ncMono）比例低。我们报道了在COVID-19中从经典单核细胞到ncMono的细胞转变下调，并且在严重疾病中ncMono中CXCL10表达降低。细胞-细胞通讯分析推断，在严重的COVID-19中，涉及ncMono的细胞相互作用减少。患者的质母细胞中BCR克隆扩增明显。通过COVID-19全基因组关联研究确定的推定疾病基因在单核细胞和树突状细胞中显示细胞类型特异性表达。IFNAR2位点（rs13050728）上的covid -19相关风险变异具有上下文特异性和单核细胞特异性表达数量性状位点效应。我们的研究强调了先天免疫细胞在COVID-19严重程度中的生物学和宿主遗传参与。采用单细胞转录组学方法分析了73名日本冠状病毒病2019 （COVID-19）患者和75名健康对照者的外周血单核细胞。将这些数据与基因分型数据相结合，突出了宿主遗传学与调节疾病严重程度的免疫反应之间的相互作用。
Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity. Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.
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影响因子：
14.9
作者：
Ghoussaini M;Mountjoy E;Carmona M;Peat G;Schmidt EM;Hercules A;Fumis L;Miranda A;Carvalho-Silva D;Buniello A;Burdett T;Hayhurst J;Baker J;Ferrer J;Gonzalez-Uriarte A;Jupp S;Karim MA;Koscielny G;Machlitt-Northen S;Malangone C;Pendlington ZM;Roncaglia P;Suveges D;Wright D;Vrousgou O;Papa E;Parkinson H;MacArthur JAL;Todd JA;Barrett JC;Schwartzentruber J;Hulcoop DG;Ochoa D;McDonagh EM;Dunham I
通讯作者：
Dunham I
影响因子：
64.5
作者：
COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium. Electronic address: julian.knight@well.ox.ac.uk;COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium
通讯作者：
COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
12.3
作者：
Lun AT;Bach K;Marioni JC
通讯作者：
Marioni JC
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin