Header

UZH-Logo

Maintenance Infos

Common features of regulatory T cell specialization during Th1 responses


Abstract

CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 immune responses, co-expression of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to control Th1 responses. T-bet-dependent expression of CXCR3 directs Treg cells to the site of inflammation. However, the suppressive mediators enabling effective control of Th1 responses at this site are unknown. In this study, we determined the signature of CXCR3+ Treg cells arising in Th1 settings and defined universal features of Treg cells in this context using multiple Th1-dominated infection models. Our analysis defined a set of Th1-specific co-inhibitory receptors and cytotoxic molecules that are specifically expressed in Treg cells during Th1 immune responses in mice and humans. Among these, we identified the novel co-inhibitory receptor CD85k as a functional predictor for Treg-mediated suppression specifically of Th1 responses, which could be explored therapeutically for selective immune suppression in autoimmunity.

Abstract

CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 immune responses, co-expression of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to control Th1 responses. T-bet-dependent expression of CXCR3 directs Treg cells to the site of inflammation. However, the suppressive mediators enabling effective control of Th1 responses at this site are unknown. In this study, we determined the signature of CXCR3+ Treg cells arising in Th1 settings and defined universal features of Treg cells in this context using multiple Th1-dominated infection models. Our analysis defined a set of Th1-specific co-inhibitory receptors and cytotoxic molecules that are specifically expressed in Treg cells during Th1 immune responses in mice and humans. Among these, we identified the novel co-inhibitory receptor CD85k as a functional predictor for Treg-mediated suppression specifically of Th1 responses, which could be explored therapeutically for selective immune suppression in autoimmunity.

Statistics

Citations

Dimensions.ai Metrics
2 citations in Web of Science®
1 citation in Scopus®
Google Scholar™

Altmetrics

Downloads

24 downloads since deposited on 23 Jul 2018
24 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:CD85k, CXCR3, Lag-3, T-bet, Th1, Treg cells, co-inhibitory receptors
Language:English
Date:2018
Deposited On:23 Jul 2018 16:54
Last Modified:19 Aug 2018 15:58
Publisher:Frontiers Research Foundation
ISSN:1664-3224
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fimmu.2018.01344
PubMed ID:29951069
Project Information:
  • : FunderSNSF
  • : Grant IDPP00P3_150663
  • : Project TitleImmune Regulation through Infection History
  • : FunderH2020
  • : Grant ID677200
  • : Project TitleImmune Regulation - How Infection History Shapes the Immune System: Pathogen-induced Changes in Regulatory T Cells

Download

Download PDF  'Common features of regulatory T cell specialization during Th1 responses'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 8MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)