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Rapid expansion of Treg cells protects from collateral colitis following a viral trigger


Schorer, Michelle; Lambert, Katharina; Rakebrandt, Nikolas; Rost, Felix; Kao, Kung-Chi; Yermanos, Alexander; Spörri, Roman; Oderbolz, Josua; Raeber, Miro E; Keller, Christian W; Lünemann, Jan D; Rogler, Gerhard; Boyman, Onur; Oxenius, Annette; Joller, Nicole (2020). Rapid expansion of Treg cells protects from collateral colitis following a viral trigger. Nature Communications, 11:1522.

Abstract

Foxp3+ regulatory T (Treg) cells are essential for maintaining peripheral tolerance and preventing autoimmunity. While genetic factors may predispose for autoimmunity, additional environmental triggers, such as viral infections, are usually required to initiate the onset of disease. Here, we show that viral infection with LCMV results in type I IFN-dependent Treg cell loss that is rapidly compensated by the conversion and expansion of Vβ5+ conventional T cells into iTreg cells. Using Vβ5-deficient mice, we show that these Vβ5+ iTreg cells are dispensable for limiting anti-viral immunity. Rather, the delayed replenishment of Treg cells in Vβ5-deficient mice compromises suppression of microbiota-dependent activation of CD8+ T cells, resulting in colitis. Importantly, recovery from clinical symptoms in IBD patients is marked by expansion of the corresponding Vβ2+ Treg population in humans. Collectively, we provide a link between a viral trigger and an impaired Treg cell compartment resulting in the initiation of immune pathology.

Abstract

Foxp3+ regulatory T (Treg) cells are essential for maintaining peripheral tolerance and preventing autoimmunity. While genetic factors may predispose for autoimmunity, additional environmental triggers, such as viral infections, are usually required to initiate the onset of disease. Here, we show that viral infection with LCMV results in type I IFN-dependent Treg cell loss that is rapidly compensated by the conversion and expansion of Vβ5+ conventional T cells into iTreg cells. Using Vβ5-deficient mice, we show that these Vβ5+ iTreg cells are dispensable for limiting anti-viral immunity. Rather, the delayed replenishment of Treg cells in Vβ5-deficient mice compromises suppression of microbiota-dependent activation of CD8+ T cells, resulting in colitis. Importantly, recovery from clinical symptoms in IBD patients is marked by expansion of the corresponding Vβ2+ Treg population in humans. Collectively, we provide a link between a viral trigger and an impaired Treg cell compartment resulting in the initiation of immune pathology.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Physical Sciences > General Chemistry
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Physical Sciences > General Physics and Astronomy
Uncontrolled Keywords:immune regulation, viral infection, colitis, type I IFN
Language:English
Date:2020
Deposited On:27 Mar 2020 07:40
Last Modified:22 Apr 2020 23:21
Publisher:Nature Publishing Group
ISSN:2041-1723
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41467-020-15309-6
Project Information:
  • : FunderSNSF
  • : Grant IDPP00P3_150663
  • : Project TitleImmune Regulation through Infection History
  • : FunderSNSF
  • : Grant IDPP00P3_181037
  • : Project TitleImmune Regulation through Infection History
  • : FunderH2020
  • : Grant ID677200
  • : Project TitleHow Infection History Shapes the Immune System: Pathogen-induced Changes in Regulatory T Cells
  • : FunderZUNIV-FAN
  • : Grant ID
  • : Project Title
  • : FunderNovartis Foundation for medical-biological research
  • : Grant ID17A027
  • : Project Title
  • : FunderUZH
  • : Grant ID
  • : Project TitleForschungskredit
  • : FunderCRPP
  • : Grant IDCYTIMM-Z
  • : Project Title

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