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DOI 10.1038/s41467-021-24981-1

Медицинская библиотека · Nature communications · 2021

Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children.

Beckmann Noam D, Comella Phillip H, Cheng Esther, Lepow Lauren, Beckmann Aviva G, Tyler Scott R, Mouskas Konstantinos, Simons Nicole W, Hoffman Gabriel E, Francoeur Nancy J, Del Valle Diane Marie, Kang Gurpawan, Do Anh, Moya Emily, Wilkins Lillian, Le Berichel Jessica, Chang Christie, Marvin Robert, Calorossi Sharlene, Lansky Alona, Walker Laura, Yi Nancy, Yu Alex, Chung Jonathan, Hartnett Matthew, Eaton Melody, Hatem Sandra, Jamal Hajra, Akyatan Alara, Tabachnikova Alexandra, Liharska Lora E, Cotter Liam, Fennessy Brian, Vaid Akhil, Barturen Guillermo, Shah Hardik, Wang Ying-Chih, Sridhar Shwetha Hara, Soto Juan, Bose Swaroop, Madrid Kent, Ellis Ethan, Merzier Elyze, Vlachos Konstantinos, Fishman Nataly, Tin Manying, Smith Melissa, Xie Hui, Patel Manishkumar, Nie Kai, Argueta Kimberly, Harris Jocelyn, Karekar Neha, Batchelor Craig, Lacunza Jose, Yishak Mahlet, Tuballes Kevin, Scott Ieisha, Kumar Arvind, Jaladanki Suraj, Agashe Charuta, Thompson Ryan, Clark Evan, Losic Bojan, Peters Lauren, Mount Sinai COVID-19 Biobank Team, Roussos Panagiotis, Zhu Jun, Wang Wenhui, Kasarskis Andrew, Glicksberg Benjamin S, Nadkarni Girish, Bogunovic Dusan, Elaiho Cordelia, Gangadharan Sandeep, Ofori-Amanfo George, Alesso-Carra Kasey, Onel Kenan, Wilson Karen M, Argmann Carmen, Bunyavanich Supinda, Alarcón-Riquelme Marta E, Marron Thomas U, Rahman Adeeb, Kim-Schulze Seunghee, Gnjatic Sacha, Gelb Bruce D, Merad Miriam, Sebra Robert, Schadt Eric E, Charney Alexander W

СтатьяПоддержка NIH: внешняя программаПеревод в очереди

Аннотация

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C.

Для цитирования: Beckmann Noam D, Comella Phillip H, Cheng Esther, Lepow Lauren, Beckmann Aviva G, Tyler Scott R, Mouskas Konstantinos, Simons Nicole W, Hoffman Gabriel E, Francoeur Nancy J, Del Valle Diane Marie, Kang Gurpawan, Do Anh, Moya Emily, Wilkins Lillian, Le Berichel Jessica, Chang Christie, Marvin Robert, Calorossi Sharlene, Lansky Alona, Walker Laura, Yi Nancy, Yu Alex, Chung Jonathan, Hartnett Matthew, Eaton Melody, Hatem Sandra, Jamal Hajra, Akyatan Alara, Tabachnikova Alexandra, Liharska Lora E, Cotter Liam, Fennessy Brian, Vaid Akhil, Barturen Guillermo, Shah Hardik, Wang Ying-Chih, Sridhar Shwetha Hara, Soto Juan, Bose Swaroop, Madrid Kent, Ellis Ethan, Merzier Elyze, Vlachos Konstantinos, Fishman Nataly, Tin Manying, Smith Melissa, Xie Hui, Patel Manishkumar, Nie Kai, Argueta Kimberly, Harris Jocelyn, Karekar Neha, Batchelor Craig, Lacunza Jose, Yishak Mahlet, Tuballes Kevin, Scott Ieisha, Kumar Arvind, Jaladanki Suraj, Agashe Charuta, Thompson Ryan, Clark Evan, Losic Bojan, Peters Lauren, Mount Sinai COVID-19 Biobank Team, Roussos Panagiotis, Zhu Jun, Wang Wenhui, Kasarskis Andrew, Glicksberg Benjamin S, Nadkarni Girish, Bogunovic Dusan, Elaiho Cordelia, Gangadharan Sandeep, Ofori-Amanfo George, Alesso-Carra Kasey, Onel Kenan, Wilson Karen M, Argmann Carmen, Bunyavanich Supinda, Alarcón-Riquelme Marta E, Marron Thomas U, Rahman Adeeb, Kim-Schulze Seunghee, Gnjatic Sacha, Gelb Bruce D, Merad Miriam, Sebra Robert, Schadt Eric E, Charney Alexander W. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children.. Nature communications. 2021. DOI: 10.1038/s41467-021-24981-1.

Предметные рубрики MeSH

AdolescentCD56 AntigenCD57 AntigensCD8-Positive T-LymphocytesCOVID-19ChildChild, PreschoolDown-RegulationFemaleHumansInfantInfant, NewbornKiller Cells, NaturalMaleMucocutaneous Lymph Node SyndromeSARS-CoV-2Systemic Inflammatory Response SyndromeTranscriptomeYoung Adult
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