학술논문
Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children.
Document Type
Author
Beckmann ND; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Comella PH; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Cheng E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Lepow L; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Beckmann AG; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Mouskas K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Simons NW; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Hoffman GE; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Francoeur NJ; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Del Valle DM; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Kang G; Department of Medicine, division of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Moya E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Wilkins L; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Le Berichel J; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Chang C; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Marvin R; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Calorossi S; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Lansky A; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Walker L; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Yi N; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Yu A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Hartnett M; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Eaton M; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Hatem S; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Jamal H; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Akyatan A; Department of of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Tabachnikova A; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Liharska LE; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Cotter L; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Fennessey B; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Vaid A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Barturen G; Department of Medical Genomics, Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government (GENYO), 18007 Urb. los Vergeles, Granada, Spain.; Tyler SR; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Shah H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Wang YC; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Sridhar SH; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Soto J; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Bose S; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Madrid K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Ellis E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Merzier E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Vlachos K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Fishman N; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Tin M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Smith M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Xie H; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Patel M; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Argueta K; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Harris J; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Karekar N; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Batchelor C; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Lacunza J; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Yishak M; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Tuballes K; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Scott L; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Kumar A; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Jaladanki S; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Thompson R; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Clark E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Losic B; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Zhu J; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Wang W; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Kasarskis A; Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Glicksberg BS; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Nadkarni G; Mount Sinai COVID Informatics Center, New York, NY 10029, USA.; Department of Medicine, Mount Sinai, New York, NY 10029, USA.; Hasso Plattner Institute for Digital Health at Mount Sinai, New York, NY 10029, USA.; Charles Bronfman Institute for Personalized Medicine, New York, NY 10029, USA.; Bogunovic D; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Elaiho C; Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Gangadharan S; Departments of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Ofori-Amanfo G; Departments of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Alesso-Carra K; Departments of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Onel K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Departments of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Wilson KM; Departments of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Argmann C; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Alarcón-Riquelme ME; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Marron TU; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Rahman A; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Kim-Schulze S; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Gnjatic S; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Medicine, division of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Gelb BD; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Departments of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.; Mindich Child Health and Development Institute at Mount Sinai, New York, NY 10029, USA.; Merad M; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Sebra R; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Black Family Stem Cell Institute, New York, NY 10029, USA.; Sema4, a Mount Sinai venture, Stamford CT, 06902, USA.; Schadt EE; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Sema4, a Mount Sinai venture, Stamford CT, 06902, USA.; Charney AW; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Institute of Data Science and Genomics Technology, New York, NY 10029.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Mount Sinai COVID Informatics Center, New York, NY 10029, USA.
Source
Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8 + T-cells and CD56 dim CD57 + NK cells. Bayesian network analyses revealed nine key regulators of this module, including TBX21 , a central coordinator of exhausted CD8 + T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.