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

Michelle Schorer; Katharina Lambert; Nikolas Rakebrandt; Felix Rost; Kung-Chi Kao; Alexander Yermanos; Roman Spörri; Josua Oderbolz; Miro E Raeber; Christian W Keller; Jan D Lünemann; Gerhard Rogler; Onur Boyman; Annette Oxenius; Nicole Joller

doi:10.1038/s41467-020-15309-6

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

Michelle Schorer, Katharina Lambert, Nikolas Rakebrandt, Felix Rost, Kung-Chi Kao, Alexander Yermanos, Roman Spörri, Josua Oderbolz, Miro E Raeber, Christian W Keller, Jan D Lünemann, Gerhard Rogler, Onur Boyman, Annette Oxenius, Nicole Joller

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	1522
Pages (from-to)	1522
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15309-6
Publication status	Published - 23 Mar 2020
Externally published	Yes

Keywords

Animals
Arenaviridae Infections/complications
Autoimmunity
CD8-Positive T-Lymphocytes/immunology
Cell Line
Colitis/immunology
Colon/immunology
Forkhead Transcription Factors/metabolism
Gastrointestinal Microbiome/immunology
Healthy Volunteers
Host Microbial Interactions/immunology
Humans
Interferon Type I/immunology
Intestinal Mucosa/immunology
Lymphocyte Activation/genetics
Lymphocytic choriomeningitis virus/immunology
Male
Mice
Mice, Knockout
Receptors, Antigen, T-Cell, alpha-beta/genetics
T-Lymphocytes, Regulatory/immunology

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10.1038/s41467-020-15309-6

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Schorer, M., Lambert, K., Rakebrandt, N., Rost, F., Kao, K.-C., Yermanos, A., Spörri, R., Oderbolz, J., Raeber, M. E., Keller, C. W., Lünemann, J. D., Rogler, G., Boyman, O., Oxenius, A., & Joller, N. (2020). Rapid expansion of Treg cells protects from collateral colitis following a viral trigger. Nature Communications, 11(1), 1522. Article 1522. https://doi.org/10.1038/s41467-020-15309-6

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title = "Rapid expansion of Treg cells protects from collateral colitis following a viral trigger",

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.",

keywords = "Animals, Arenaviridae Infections/complications, Autoimmunity, CD8-Positive T-Lymphocytes/immunology, Cell Line, Colitis/immunology, Colon/immunology, Forkhead Transcription Factors/metabolism, Gastrointestinal Microbiome/immunology, Healthy Volunteers, Host Microbial Interactions/immunology, Humans, Interferon Type I/immunology, Intestinal Mucosa/immunology, Lymphocyte Activation/genetics, Lymphocytic choriomeningitis virus/immunology, Male, Mice, Mice, Knockout, Receptors, Antigen, T-Cell, alpha-beta/genetics, T-Lymphocytes, Regulatory/immunology",

author = "Michelle Schorer and Katharina Lambert and Nikolas Rakebrandt and Felix Rost and Kung-Chi Kao and Alexander Yermanos and Roman Sp{\"o}rri and Josua Oderbolz and Raeber, \{Miro E\} and Keller, \{Christian W\} and L{\"u}nemann, \{Jan D\} and Gerhard Rogler and Onur Boyman and Annette Oxenius and Nicole Joller",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = mar,

day = "23",

doi = "10.1038/s41467-020-15309-6",

language = "English",

volume = "11",

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Schorer, M, Lambert, K, Rakebrandt, N, Rost, F, Kao, K-C, Yermanos, A, Spörri, R, Oderbolz, J, Raeber, ME, Keller, CW, Lünemann, JD, Rogler, G, Boyman, O, Oxenius, A & Joller, N 2020, 'Rapid expansion of Treg cells protects from collateral colitis following a viral trigger', Nature Communications, vol. 11, no. 1, 1522, pp. 1522. https://doi.org/10.1038/s41467-020-15309-6

TY - JOUR

T1 - Rapid expansion of Treg cells protects from collateral colitis following a viral trigger

AU - Schorer, Michelle

AU - Lambert, Katharina

AU - Rakebrandt, Nikolas

AU - Rost, Felix

AU - Kao, Kung-Chi

AU - Yermanos, Alexander

AU - Spörri, Roman

AU - Oderbolz, Josua

AU - Raeber, Miro E

AU - Keller, Christian W

AU - Lünemann, Jan D

AU - Rogler, Gerhard

AU - Boyman, Onur

AU - Oxenius, Annette

AU - Joller, Nicole

PY - 2020/3/23

Y1 - 2020/3/23

N2 - 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.

AB - 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.

KW - Animals

KW - Arenaviridae Infections/complications

KW - Autoimmunity

KW - CD8-Positive T-Lymphocytes/immunology

KW - Cell Line

KW - Colitis/immunology

KW - Colon/immunology

KW - Forkhead Transcription Factors/metabolism

KW - Gastrointestinal Microbiome/immunology

KW - Healthy Volunteers

KW - Host Microbial Interactions/immunology

KW - Humans

KW - Interferon Type I/immunology

KW - Intestinal Mucosa/immunology

KW - Lymphocyte Activation/genetics

KW - Lymphocytic choriomeningitis virus/immunology

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Receptors, Antigen, T-Cell, alpha-beta/genetics

KW - T-Lymphocytes, Regulatory/immunology

U2 - 10.1038/s41467-020-15309-6

DO - 10.1038/s41467-020-15309-6

M3 - Article

C2 - 32251280

SN - 2041-1723

VL - 11

SP - 1522

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1522

ER -

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

Abstract

Keywords

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