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Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells.
Sumida, Tomokazu S; Dulberg, Shai; Schupp, Jonas C; Lincoln, Matthew R; Stillwell, Helen A; Axisa, Pierre-Paul; Comi, Michela; Unterman, Avraham; Kaminski, Naftali; Madi, Asaf; Kuchroo, Vijay K; Hafler, David A.
  • Sumida TS; Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, USA. tomokazu.sumida@yale.edu.
  • Dulberg S; Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Schupp JC; Section of Pulmonary, Critical Care and Sleep Medicine Section, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Lincoln MR; Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease Hannover, German Lung Research Center, Hannover, Germany.
  • Stillwell HA; Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Axisa PP; Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
  • Comi M; Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Unterman A; Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Kaminski N; Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, USA.
  • Madi A; Section of Pulmonary, Critical Care and Sleep Medicine Section, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
  • Kuchroo VK; Pulmonary Institute, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
  • Hafler DA; Section of Pulmonary, Critical Care and Sleep Medicine Section, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Nat Immunol ; 23(4): 632-642, 2022 04.
Article in English | MEDLINE | ID: covidwho-1751737
ABSTRACT
Although inhibition of T cell coinhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. In the present study, we show that type 1 interferon (IFN-I) regulates coinhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses established the dynamic regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors (TFs) and TF footprint analysis revealed two regulator modules with different temporal kinetics that control expression of coinhibitory receptors and IFN-I response genes, with SP140 highlighted as one of the key regulators that differentiates LAG-3 and TIGIT expression. Finally, we found that the dynamic IFN-I response in vitro closely mirrored T cell features in acute SARS-CoV-2 infection. The identification of unique TFs controlling coinhibitory receptor expression under IFN-I response may provide targets for enhancement of immunotherapy in cancer, infectious diseases and autoimmunity.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferon Type I / COVID-19 Limits: Humans Language: English Journal: Nat Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41590-022-01152-y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferon Type I / COVID-19 Limits: Humans Language: English Journal: Nat Immunol Journal subject: Allergy and Immunology Year: 2022 Document Type: Article Affiliation country: S41590-022-01152-y