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Weill Cornell Medicine

Cell, 2023 Aug 15;S0092-8674(23)00796-1 | https://doi.org/10.1016/j.cell.2023.07.019 Epigenetic memory of coronavirus infection in innate immune cells and their progenitors

Jin-Gyu Cheong,^1,2 Arjun Ravishankar,^1,22 Siddhartha Sharma,^3,22 Christopher N. Parkhurst,^5,22 Simon A. Grassmann,⁶Claire K. Wingert,⁶ Paoline Laurent,⁷ Sai Ma,^8,9 Lucinda Paddock,¹ Isabella C. Miranda,⁵ Emin Onur Karakaslar,^3,21Djamel Nehar-Belaid,³ Asa Thibodeau,³ Michael J. Bale,^1,2 Vinay K. Kartha,^8,9 Jim K. Yee,¹ Minh Y. Mays,¹Chenyang Jiang,¹ Andrew W. Daman,^1,2 Alexia Martinez de Paz,¹ Dughan Ahimovic,^1,2 Victor Ramos,¹⁰Alexander Lercher,¹⁰ Erik Nielsen,^1,5 Sergio Alvarez-Mulett,⁵ Ling Zheng,¹ Andrew Earl,^8,9 Alisha Yallowitz,¹Lexi Robbins,¹ Elyse LaFond,¹¹ Karissa L. Weidman,⁵ Sabrina Racine Brzostek,¹ He S. Yang,¹ David R. Price,⁵Louise Leyre,² Andre´ F. Rendeiro,^12,13,14 Hiranmayi Ravichandran,^13,15 Junbum Kim,¹² Alain C. Borczuk,^1,16Charles M. Rice,¹⁰ R. Brad Jones,^17,18Edward J. Schenck,⁵ Robert J. Kaner,¹⁹ Amy Chadburn,¹ Zhen Zhao,¹Virginia Pascual,²⁰Olivier Elemento,^12,13 Robert E. Schwartz,⁵ Jason D. Buenrostro,^8,9 Rachel E. Niec,^5,10Franck J. Barrat,^2,7,18 Lindsay Lief,⁵ Joseph C. Sun,⁶ Duygu Ucar,^3,4,* and Steven Z. Josefowicz^1,2,23,24,*

¹Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA
²Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, NY 10065, USA
³The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA
⁴Institute for Systems Genomics, University of Connecticut Health Center, Farmington, CT, USA
⁵Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
⁶Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
⁷HSS Research Institute, Hospital for Special Surgery, New York, NY 10021, USA
⁸Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
⁹Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02142, USA
¹⁰The Rockefeller University, New York, NY 10065, USA
¹¹NYU Langone Health, New York, NY 10016, USA
¹²Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA
¹³Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10065, USA
¹⁴CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, 1090 Vienna, Austria
¹⁵Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, USA
¹⁶Department of Pathology and Laboratory Medicine, Northwell Health, Greenvale, NY 11548, USA
¹⁷Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY 10065, USA
¹⁸Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA
¹⁹Department of Genetic Medicine, Weill Cornell Medicine, New York, NY 10065, USA
²⁰Department of Pediatrics, Gale and Ira Drukier Institute for Children’s Health, Weill Cornell Medicine, New York, NY 10065, USA
²¹Leiden University Medical Center (LUMC), Leiden, The Netherlands
²²These authors contributed equally
²³Senior author
²⁴Lead contact

^*Corresponding author: correspondence to Duygu Ucar or Steven Z. Josefowicz

Abstract

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

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형식Research article
게재일2023년 08월 (BRIC 등록일 2023-08-21)
연구진국외 연구진
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