TIGIT limits immune pathology during viral infections

Michelle Schorer, Nikolas Rakebrandt, Katharina Lambert, Annika Hunziker, Katharina Pallmer, Annette Oxenius, Anja Kipar, Silke Stertz and Nicole Joller ()
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Michelle Schorer: University of Zurich
Nikolas Rakebrandt: University of Zurich
Katharina Lambert: University of Zurich
Annika Hunziker: University of Zurich
Katharina Pallmer: Institute of Microbiology, ETH Zurich
Annette Oxenius: Institute of Microbiology, ETH Zurich
Anja Kipar: University of Zurich
Silke Stertz: University of Zurich
Nicole Joller: University of Zurich

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Co-inhibitory pathways have a fundamental function in regulating T cell responses and control the balance between promoting efficient effector functions and restricting immune pathology. The TIGIT pathway has been implicated in promoting T cell dysfunction in chronic viral infection. Importantly, TIGIT signaling is functionally linked to IL-10 expression, which has an effect on both virus control and maintenance of tissue homeostasis. However, whether TIGIT has a function in viral persistence or limiting tissue pathology is unclear. Here we report that TIGIT modulation effectively alters the phenotype and cytokine profile of T cells during influenza and chronic LCMV infection, but does not affect virus control in vivo. Instead, TIGIT has an important effect in limiting immune pathology in peripheral organs by inducing IL-10. Our data therefore identify a function of TIGIT in limiting immune pathology that is independent of viral clearance.

Date: 2020
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DOI: 10.1038/s41467-020-15025-1

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