本期文章：《细胞》：Online/在线发表

美国威尔康奈尔医学院Steven Z. Josefowicz和康涅狄格大学健康中心Duygu Ucar研究团队，揭示了存在于先天免疫细胞及其祖细胞（HSPC）中的冠状病毒感染表观遗传记忆。2023年8月18日出版的《细胞》杂志发表了这项成果。

研究人员从外周血富集的循环HSPC中发现了骨髓HSPC多样性，从而能够研究其在2019年冠状病毒（COVID-19）感染后的表观基因组重编程。HSPC先天免疫表型和表观遗传程序的改变在重症COVID-19患者体内可持续存在数月至1年，并与不同的转录因子（TF）活性、炎症程序调节改变和骨髓生成持续增加有关。HSPC表观基因组改变通过分化传递到后代先天免疫细胞。

IL-6的早期活性与人COVID-19和小鼠冠状病毒感染模型中这些表型的持续存在有关。HSPC的表观遗传重编程可能是病毒感染后免疫功能改变的基础且具有广泛的相关性，特别是对于数百万COVID-19的幸存者而言。

据悉，炎症可以在免疫和非免疫细胞中诱发持久表型。尚不清楚人类感染和相关炎症是否以及如何在造血干细胞和祖细胞中形成先天免疫记忆。

附：英文原文

Title: Epigenetic memory of coronavirus infection in innate immune cells and their progenitors

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

Issue&Volume: 2023-08-18

Abstract: Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whetherand how human infections and associated inflammation can form innate immune memoryin hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found thatcirculating HSPC, enriched from peripheral blood, captured the diversity of bone marrowHSPC, enabling investigation of their epigenomic reprogramming following coronavirusdisease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programsof HSPC persisted for months to 1 year following severe COVID-19 and were associatedwith distinct transcription factor (TF) activities, altered regulation of inflammatoryprograms, and durable increases in myelopoiesis. HSPC epigenomic alterations wereconveyed, through differentiation, to progeny innate immune cells. Early activityof IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirusinfection model. Epigenetic reprogramming of HSPC may underlie altered immune functionfollowing infection and be broadly relevant, especially for millions of COVID-19 survivors.

DOI: 10.1016/j.cell.2023.07.019