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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 V?5+ conventional T cells into iTreg cells. Using V?5-deficient mice, we show that these V?5+ iTreg cells are dispensable for limiting anti-viral immunity. Rather, the delayed replenishment of Treg cells in V?5-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 V?2+ 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.

SUBMITTER: Schorer M

PROVIDER: S-EPMC7090079 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Schorer Michelle M Lambert Katharina K Rakebrandt Nikolas N Rost Felix F Kao Kung-Chi KC Yermanos Alexander A Spörri Roman R Oderbolz Josua J Raeber Miro E ME Keller Christian W CW Lünemann Jan D JD Rogler Gerhard G Boyman Onur O Oxenius Annette A Joller Nicole N

Nature communications 20200323 1

Foxp3<sup>+</sup> 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<sup>+</sup> conventional T cells into iTreg ce ...[more]

PMID: 32251280

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Project description:In December 2019, rising pneumonia cases caused by a novel β-coronavirus (SARS-CoV-2) occurred in Wuhan, China, which has rapidly spread worldwide, causing thousands of deaths. The WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern, since then several scientists are dedicated to its study. It has been observed that many human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on the host cell machinery for the replication and co-evolution. In this work, we analysed 91 molecular features and codon usage patterns for 339 viral genes and 463 human genes that consisted of 677,873 codon positions. Hereby, we selected the highly expressed genes from human lung tissue to perform computational studies that permit to compare their molecular features with those of SARS, SARS-CoV-2 and MERS genes. The integrated analysis of all the features revealed that certain viral genes and overexpressed human genes have similar codon usage patterns. The main pattern was the A/T bias that together with other features could propitiate the viral infection, enhanced by a host dependant specialization of the translation machinery of only some of the overexpressed genes. The envelope protein E, the membrane glycoprotein M and ORF7 could be further benefited. This could be the key for a facilitated translation and viral replication conducting to different comorbidities depending on the genetic variability of population due to the host translation machinery. This is the first codon usage approach that reveals which human genes could be potentially deregulated due to the codon usage similarities between the host and the viral genes when the virus is already inside the human cells of the lung tissues. Our work leaded to the identification of additional highly expressed human genes which are not the usual suspects but might play a role in the viral infection and settle the basis for further research in the field of human genetics associated with new viral infections. To identify the genes that could be deregulated under a viral infection is important to predict the collateral effects and determine which individuals would be more susceptible based on their genetic features and comorbidities associated.

Dataset Information

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

Publications

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

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