Published In

Immunohorizons

Document Type

Article

Publication Date

8-2023

Subjects

Cell Developement -- Biology

Abstract

The E3 ubiquitin ligase cullin 3 (Cul3) is critical for invariant NKT (iNKT) cell development, as iNKT cells lacking Cul3 accumulate in the immature developmental stages. However, the mechanisms by which Cul3 mediates iNKT cell development remain unknown. In this study, we investigated the role of Cul3 in both immature and mature thymic iNKT cells using a mouse model with a T cell–specific deletion of Cul3. We found that mature iNKT cells lacking Cul3 proliferated and died more than wild-type cells did. These cells also displayed increased glucose metabolism and autophagy. Interestingly, we found that tight regulation of iron homeostasis is critical for iNKT cell development. Without Cul3, mature iNKT cells harbored higher levels of cytosolic iron, a phenotype associated with increased cell death. Taken together, our data suggest that Cul3 promotes iNKT cell development partially through intracellular iron homeostasis. ImmunoHorizons, 2023, 7: 235–242.

Rights

Copyright (c) 2023 The Authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

DOI

10.4049/immunohorizons.2300002

Persistent Identifier

https://archives.pdx.edu/ds/psu/40644

Included in

Biology Commons

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