دورية أكاديمية
A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling.
العنوان: | A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling. |
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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.) |
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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 |
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