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The thioredoxin-1 inhibitor Txnip restrains effector T-cell and germinal center B-cell expansion.

Authors
  • Muri, Jonathan1
  • Thut, Helen1
  • Kopf, Manfred1
  • 1 Institute of Molecular Health Sciences, ETH Zürich, Zürich, Switzerland. , (Switzerland)
Type
Published Article
Journal
European Journal of Immunology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Sep 09, 2020
Identifiers
DOI: 10.1002/eji.202048851
PMID: 32902872
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Thioredoxin-1 (Trx1) is a vital component for cellular redox homeostasis. In T cells, Trx1 donates electrons for the de novo synthesis of deoxyribonucleotides to allow rapid cell proliferation. The Trx-interacting protein (Txnip) binds to the reduced Trx1 and inhibits its activity. However, the role of Txnip in adaptive immunity in vivo is unknown. Here, we show that absence of Txnip increased proliferation of effector T cells and GC B-cell responses in response to lymphocytic choriomeningitis virus and Qβ virus-like particles, respectively, but did not affect development and homeostasis of T and B cells. While downregulation of Txnip and concomitant upregulation of Trx1 is critical for rapid T-cell expansion upon viral infection, re-expression of Txnip and consequently inhibition of Trx1 is important to restrain late T-cell expansion. Importantly, we demonstrated that T-cell receptor (TCR) engagement but not CD28 costimulation is critically required for Txnip downregulation. Thus, this study further uncovers positive and negative control of lymphocyte proliferation by the Trx1 system. © 2020 Wiley-VCH GmbH.

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