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Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells
While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Here we show that type 1 interferon (IFN-I) regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989655/ https://www.ncbi.nlm.nih.gov/pubmed/35301508 http://dx.doi.org/10.1038/s41590-022-01152-y |
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author | 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. |
author_facet | 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. |
author_sort | Sumida, Tomokazu S. |
collection | PubMed |
description | While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Here we show that type 1 interferon (IFN-I) regulates co-inhibitory 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 co-inhibitory 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 co-inhibitory receptor expression under IFN-I response may provide targets for enhancement of immunotherapy in cancer, infectious diseases, and autoimmunity. |
format | Online Article Text |
id | pubmed-8989655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
spelling | pubmed-89896552022-09-17 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. Nat Immunol Article While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Here we show that type 1 interferon (IFN-I) regulates co-inhibitory 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 co-inhibitory 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 co-inhibitory receptor expression under IFN-I response may provide targets for enhancement of immunotherapy in cancer, infectious diseases, and autoimmunity. 2022-04 2022-03-17 /pmc/articles/PMC8989655/ /pubmed/35301508 http://dx.doi.org/10.1038/s41590-022-01152-y Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: |
spellingShingle | Article 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. Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells |
title | Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells |
title_full | Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells |
title_fullStr | Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells |
title_full_unstemmed | Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells |
title_short | Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells |
title_sort | type i interferon transcriptional network regulates expression of coinhibitory receptors in human t cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989655/ https://www.ncbi.nlm.nih.gov/pubmed/35301508 http://dx.doi.org/10.1038/s41590-022-01152-y |
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