Rapid Expansion of Treg Cells Protects from Collateral Colitis Following a Viral Trigger

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Apr 7

PMID 32251280

Citations 14

Authors

Michelle Schorer

Katharina Lambert

Nikolas Rakebrandt

Felix Rost

Kung-Chi Kao

Alexander Yermanos

Roman Sporri

Josua Oderbolz

Miro E Raeber

Christian W Keller

Jan D Lunemann

Gerhard Rogler

Onur Boyman

Annette Oxenius

Nicole Joller

Affiliations

Soon will be listed here.

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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