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10.1038/s41590-022-01152-y

http://scihub22266oqcxt.onion/10.1038/s41590-022-01152-y
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suck abstract from ncbi


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pmid35301508      Nat+Immunol 2022 ; 23 (4): 632-642
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  • Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells #MMPMID35301508
  • Sumida TS; Dulberg S; Schupp JC; Lincoln MR; Stillwell HA; Axisa PP; Comi M; Unterman A; Kaminski N; Madi A; Kuchroo VK; Hafler DA
  • Nat Immunol 2022[Apr]; 23 (4): 632-642 PMID35301508show ga
  • 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.
  • |*COVID-19[MESH]
  • |*Interferon Type I/genetics[MESH]
  • |Gene Regulatory Networks[MESH]
  • |Humans[MESH]
  • |Receptors, Antigen, T-Cell/metabolism[MESH]
  • |Receptors, Immunologic/genetics[MESH]
  • |SARS-CoV-2[MESH]


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