Ndfip1 Restricts Th17 Cell Potency by Limiting Lineage Stability and Proinflammatory Cytokine Production

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jan 5

PMID 28051111

Citations 12

Authors

Awo Akosua Layman

Stephanie Sprout

Dylan Phillips

Paula M Oliver

Affiliations

Soon will be listed here.

Abstract

While Th17 cells can protect against colonization by pathogenic organisms, they also have the potential to become pathogenic and promote autoimmune and inflammatory diseases. Mechanisms that control their pathogenic potential remain poorly understood. Here we show that Ndfip1, a co-activator of the E3 ubiquitin ligase Itch, restricts the frequency and pathogenicity of Th17 cells. Mice lacking Ndfip1 have increased numbers of Th17 cells, and this increase is cell intrinsic. We found that Ndfip1 restricts production of the proinflammatory cytokines in Th17 cells. Increased cytokine production correlated with reduced degradation and accumulation of RORγT. When transferred in vivo, Th17 cells lacking Ndfip1 were more likely to maintain their ability to make IL-17, were more potent proinflammatory cytokine producers, and were powerful inducers of colitis. Together our data support an essential role for Ndfip1 in degrading RORγT and suppressing Th17 lineage stability, proinflammatory cytokine production, and pathogenicity.

Citing Articles

RORγt protein modifications and IL-17-mediated inflammation.

Kumar R, Theiss A, Venuprasad K Trends Immunol. 2021; 42(11):1037-1050.

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The Ubiquitin-Proteasome System in Immune Cells.

Cetin G, Klafack S, Studencka-Turski M, Kruger E, Ebstein F Biomolecules. 2021; 11(1).

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Itch attenuates CD4 T-cell proliferation in mice by limiting WBP2 protein stability.

Field N, Elbulok O, Dybas J, Moser E, Dar A, Spruce L Eur J Immunol. 2020; 50(10):1468-1483.

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Collagenous Colitis Is Associated With HLA Signature and Shares Genetic Risks With Other Immune-Mediated Diseases.

Stahl E, Roda G, Dobbyn A, Hu J, Zhang Z, Westerlind H Gastroenterology. 2020; 159(2):549-561.e8.

PMID: 32371109 PMC: 7483815. DOI: 10.1053/j.gastro.2020.04.063.

Itch regulation of innate and adaptive immune responses in mice and humans.

Field N, Moser E, Oliver P J Leukoc Biol. 2020; 108(1):353-362.

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