Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells.


Journal

Research square
Titre abrégé: Res Sq
Pays: United States
ID NLM: 101768035

Informations de publication

Date de publication:
08 Jun 2021
Historique:
entrez: 15 6 2021
pubmed: 16 6 2021
medline: 16 6 2021
Statut: epublish

Résumé

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. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection. Here we show that IFN-I regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while surprisingly inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses enabled the construction of dynamic transcriptional regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors on human primary T cells revealed unique regulators that control expression of co-inhibitory receptors. We found that the dynamic IFN-I response

Identifiants

pubmed: 34127967
doi: 10.21203/rs.3.rs-133494/v1
pmc: PMC8202434
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NCI NIH HHS
ID : R01 CA227473
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS045937
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI039671
Pays : United States
Organisme : NINDS NIH HHS
ID : R25 NS079193
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA121974
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089992
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI144166
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI073748
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL145567
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141852
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS030843
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI056299
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127349
Pays : United States

Commentaires et corrections

Type : UpdateIn

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Auteurs

David Hafler (D)

Yale University.

Tomokazu Sumida (T)

Yale University School of Medicine.

Shai Dulberg (S)

Tel Aviv University.

Jonas Schupp (J)

Yale University.

Helen Stillwell (H)

Yale University.

Pierre-Paul Axisa (PP)

Yale University.

Michela Comi (M)

Department of Immunobiology, Yale University School of Medicine; Department of Neurology, Yale University School of Medicine.

Avraham Unterman (A)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine.

Asaf Madi (A)

Tel Aviv University.

Vijay Kuchroo (V)

Harvard University.

Classifications MeSH