دورية أكاديمية
أعرض في EDS

A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling.

التفاصيل البيبلوغرافية
العنوان: A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling.
المؤلفون: Hackney JA; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Shivram H; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Vander Heiden J; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Overall C; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Orozco L; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Gao X; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Kim E; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., West N; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Qamra A; Hoffman-La Roche Limited, 7070 Mississauga Road, Mississauga, ON L5N 5M8, Canada., Chang D; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Chakrabarti A; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Choy DF; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Combes AJ; University of California San Francisco, San Francisco, CA, USA., Courau T; University of California San Francisco, San Francisco, CA, USA., Fragiadakis GK; University of California San Francisco, San Francisco, CA, USA., Rao AA; University of California San Francisco, San Francisco, CA, USA., Ray A; University of California San Francisco, San Francisco, CA, USA., Tsui J; University of California San Francisco, San Francisco, CA, USA., Hu K; University of California San Francisco, San Francisco, CA, USA., Kuhn NF; University of California San Francisco, San Francisco, CA, USA., Krummel MF; University of California San Francisco, San Francisco, CA, USA., Erle DJ; University of California San Francisco, San Francisco, CA, USA., Kangelaris K; University of California San Francisco, San Francisco, CA, USA., Sarma A; University of California San Francisco, San Francisco, CA, USA., Lyon Z; University of California San Francisco, San Francisco, CA, USA., Calfee CS; University of California San Francisco, San Francisco, CA, USA., Woodruff PG; University of California San Francisco, San Francisco, CA, USA., Ghale R; University of California San Francisco, San Francisco, CA, USA., Mick E; University of California San Francisco, San Francisco, CA, USA., Byrne A; University of California San Francisco, San Francisco, CA, USA., Zha BS; University of California San Francisco, San Francisco, CA, USA., Langelier C; University of California San Francisco, San Francisco, CA, USA., Hendrickson CM; University of California San Francisco, San Francisco, CA, USA., van der Wijst MGP; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Hartoularos GC; University of California San Francisco, San Francisco, CA, USA., Grant T; University of California San Francisco, San Francisco, CA, USA., Bueno R; University of California San Francisco, San Francisco, CA, USA., Lee DS; University of California San Francisco, San Francisco, CA, USA., Greenland JR; University of California San Francisco, San Francisco, CA, USA., Sun Y; University of California San Francisco, San Francisco, CA, USA., Perez R; University of California San Francisco, San Francisco, CA, USA., Ogorodnikov A; University of California San Francisco, San Francisco, CA, USA., Ward A; University of California San Francisco, San Francisco, CA, USA., Ye CJ; University of California San Francisco, San Francisco, CA, USA., Ramalingam T; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., McBride JM; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Cai F; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Teterina A; Hoffman-La Roche Limited, 7070 Mississauga Road, Mississauga, ON L5N 5M8, Canada., Bao M; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Tsai L; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Rosas IO; Baylor College of Medicine, 7200 Cambridge St, Houston, TX 77030, USA., Regev A; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Kapadia SB; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Bauer RN; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA., Rosenberger CM; Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
مؤلفون مشاركون: UCSF COMET Consortium
المصدر: IScience [iScience] 2023 Sep 01; Vol. 26 (10), pp. 107813. Date of Electronic Publication: 2023 Sep 01 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGE hi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. IL-6 signaling blockade by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of EN-RAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.
Competing Interests: J.A.H., H.S., J.V.H., C.O., L.O., X.G., N.W., A.Q., D.C., A.C, D.F.C., T.R., J.M.M., F.C., A.T., M.B., L.T., A.R., S.B.K., R.N.B., and C.M.R. were employees of Genentech, Inc. at the time of this study and own equity in Roche. The COMET study was supported in part by Genentech funding. C.J.Y. is a scientific advisory board member for and holds equity in Related Sciences and ImmunAI, a consultant for and holds equity in Maze Therapeutics, and a consultant for TRex Bio. C.J.Y. has received research support from Chan Zuckerberg Initiative, Chan Zuckerberg Biohub, and Genentech. C.S.C. has received research funding from Roche-Genentech for an unrelated project as well as from NIH, DOD, and Quantum Leap Healthcare Collaborative. C.S.C. is a consultant for Vasomune, Quark, and GEn1E Lifesciences. C.H. is a consultant for Spring Discovery but does not have any financial interest in the company nor is the work related to what is covered in this manuscript. A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas Therapeutics and, until 31 July 2020, was a scientific advisory board member of Thermo Fisher Scientific, Syros Pharmaceuticals, Asimov, and Neogene Therapeutics. A.R. is a named inventor on multiple patents related to single-cell and spatial genomics filed by or issued to the Broad Institute.
(© 2023 The Authors.)
References: Crit Care. 2014 Aug 01;18(4):R163. (PMID: 25084831)
Genome Med. 2021 Jan 13;13(1):7. (PMID: 33441124)
Genome Biol. 2019 Mar 22;20(1):63. (PMID: 30902100)
Immunity. 2021 May 11;54(5):875-884. (PMID: 33979585)
Sci Rep. 2021 Jun 9;11(1):12174. (PMID: 34108608)
Bioinformatics. 2017 Apr 15;33(8):1179-1186. (PMID: 28088763)
Front Immunol. 2020 May 01;11:827. (PMID: 32425950)
Front Immunol. 2019 Feb 27;10:327. (PMID: 30873175)
Science. 2020 Sep 4;369(6508):1210-1220. (PMID: 32788292)
N Engl J Med. 2021 Apr 22;384(16):1503-1516. (PMID: 33631066)
J Clin Invest. 2020 May 1;130(5):2620-2629. (PMID: 32217835)
Respir Med. 2008 Apr;102(4):567-73. (PMID: 18164192)
Cell Death Dis. 2020 Oct 27;11(10):921. (PMID: 33110074)
Front Oncol. 2019 Mar 26;9:187. (PMID: 30972297)
PLoS Comput Biol. 2013;9(8):e1003118. (PMID: 23950696)
Nature. 2021 Mar;591(7848):124-130. (PMID: 33494096)
Cancer Res. 2007 Oct 15;67(20):10019-26. (PMID: 17942936)
Front Immunol. 2019 Jun 25;10:1426. (PMID: 31293586)
Nat Med. 2020 Mar;26(3):333-340. (PMID: 32066974)
J Leukoc Biol. 2007 Jan;81(1):28-37. (PMID: 16943388)
Breast Cancer Res. 2013;15(5):R79. (PMID: 24021059)
Nat Med. 2021 May;27(5):904-916. (PMID: 33879890)
Nat Med. 2020 Jun;26(6):842-844. (PMID: 32398875)
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):. (PMID: 34433692)
Nat Commun. 2021 Mar 5;12(1):1428. (PMID: 33674591)
Atherosclerosis. 2003 Dec;171(2):211-8. (PMID: 14644389)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nat Biotechnol. 2016 May;34(5):525-7. (PMID: 27043002)
J Clin Immunol. 2021 Apr;41(3):515-525. (PMID: 33387156)
Cell Rep Med. 2022 Oct 18;3(10):100779. (PMID: 36208629)
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):. (PMID: 33479167)
Nat Methods. 2015 May;12(5):453-7. (PMID: 25822800)
Nat Commun. 2021 Aug 26;12(1):5152. (PMID: 34446707)
Genome Biol. 2018 Feb 6;19(1):15. (PMID: 29409532)
Front Immunol. 2021 Jun 18;12:697405. (PMID: 34220859)
Nat Rev Immunol. 2009 Mar;9(3):162-74. (PMID: 19197294)
Cell. 2020 Nov 25;183(5):1340-1353.e16. (PMID: 33096020)
Nucleic Acids Res. 2015 Apr 20;43(7):e47. (PMID: 25605792)
Nat Rev Immunol. 2021 Aug;21(8):485-498. (PMID: 33526920)
Cell. 2021 Apr 1;184(7):1895-1913.e19. (PMID: 33657410)
Cell Immunol. 2021 Jan;359:104254. (PMID: 33296753)
Cell. 2021 Jun 24;184(13):3573-3587.e29. (PMID: 34062119)
Sci Transl Med. 2021 Jun 16;13(598):. (PMID: 34103408)
Cancer Res. 2015 Oct 1;75(19):4074-85. (PMID: 26294209)
iScience. 2021 Jan 22;24(1):101896. (PMID: 33319166)
Ann Rheum Dis. 2016 Jan;75(1):278-85. (PMID: 25371442)
Bioinformatics. 2016 Sep 15;32(18):2847-9. (PMID: 27207943)
Science. 2020 Sep 4;369(6508):. (PMID: 32669297)
Bioinformatics. 2005 Oct 15;21(20):3940-1. (PMID: 16096348)
iScience. 2023 Aug 11;26(9):107597. (PMID: 37664617)
J Clin Invest. 2001 Jun;107(12):1537-44. (PMID: 11413161)
Genome Biol. 2015 Mar 31;16:64. (PMID: 25853550)
Bioinformatics. 2010 Jan 1;26(1):139-40. (PMID: 19910308)
JCI Insight. 2021 Jun 18;6(13):. (PMID: 34143756)
Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):818-24. (PMID: 7509706)
Cell Death Differ. 2020 Nov;27(11):3196-3207. (PMID: 32514047)
Cell. 2020 Dec 10;183(6):1479-1495.e20. (PMID: 33171100)
F1000Res. 2016 Aug 31;5:2122. (PMID: 27909575)
JAMA. 2012 Jun 20;307(23):2526-33. (PMID: 22797452)
Cell Mol Immunol. 2020 May;17(5):533-535. (PMID: 32203188)
Nat Med. 2020 Jul;26(7):1070-1076. (PMID: 32514174)
Front Immunol. 2019 May 29;10:1202. (PMID: 31231374)
J Innate Immun. 2018;10(5-6):407-413. (PMID: 29945134)
J Clin Invest. 2021 Mar 15;131(6):. (PMID: 33492309)
J Clin Invest. 2021 Jan 4;131(1):. (PMID: 33119547)
Front Immunol. 2021 Jul 14;12:695972. (PMID: 34341659)
Cell. 2020 Sep 17;182(6):1419-1440.e23. (PMID: 32810438)
Cell. 2020 Sep 17;182(6):1401-1418.e18. (PMID: 32810439)
Nature. 2021 Feb;590(7847):635-641. (PMID: 33429418)
Immunity. 2020 Oct 13;53(4):864-877.e5. (PMID: 32791036)
Immunity. 2021 Apr 13;54(4):753-768.e5. (PMID: 33765435)
Methods Mol Biol. 2016;1418:283-334. (PMID: 27008021)
Nature. 2021 Jul;595(7865):107-113. (PMID: 33915569)
Crit Care Med. 2022 Mar 1;50(3):398-409. (PMID: 34612846)
Nat Commun. 2017 Jan 16;8:14049. (PMID: 28091601)
Sci Transl Med. 2021 Sep 22;13(612):eabh2624. (PMID: 34429372)
JAMA. 2021 Aug 10;326(6):499-518. (PMID: 34228774)
معلومات مُعتمدة: R35 HL140026 United States HL NHLBI NIH HHS; P30 AR070155 United States AR NIAMS NIH HHS; K23 HL133495 United States HL NHLBI NIH HHS; R01 AI136972 United States AI NIAID NIH HHS; U19 AI077439 United States AI NIAID NIH HHS; R01 AR071522 United States AR NIAMS NIH HHS; T32 CA108462 United States CA NCI NIH HHS; U01 HG012192 United States HG NHGRI NIH HHS
فهرسة مساهمة: Investigator: Y Abe-Jones; M Adkisson; KM Ansel; S Asthana; A Beagle; S Bhide; C Cai; S Caldera; M Calvo; SA Carrillo; S Chak; S Christenson; Z Collins; S Darmanis; A Detweiler; C DeVoe; W Eckalbar; J Giberson; A Gonzalez; G Gordon; PH Serpa; A Jauregui; C Jones; S Ke; D Kushnoor; T Lea; D Lee; A Leligdowicz; Y Liu; S Mahboob; L Maliskova; M Matthay; E McCarthy; P Muñoz-Sandoval; N Neff; V Nguyen; N Nigam; R Parada; M Phelps; L Pierce; P Prasad; S Rashid; G Reeder; N Rodriguez; B Samad; A Schroeder; C Shaw; A Shen; A Sigman; P Sinha; M Spitzer; S Sunshine; K Tang; LT Altamirano; A Tsitsiklis; E Tumurbaatar; V Upadhyay; A Whatley; A Willmore; M Wilson; J Winkler; K Wong; K Yee; M Yu; M Zhou; WS Zhu
Keywords: Clinical genetics; Immune response; Molecular medicine
تواريخ الأحداث: Date Created: 20231009 Latest Revision: 20240628
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10551843
DOI: 10.1016/j.isci.2023.107813
PMID: 37810211
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2023.107813