Cullin 3-Mediated Regulation of Intracellular Iron Homeostasis Promotes Thymic Invariant NKT Cell Maturation.

Autor:	Yarosz EL; Immunology Graduate Program, University of Michigan Medical School, Ann Arbor, MI., Kumar A; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI., Singer JD; Department of Biology, Portland State University, Portland, OR., Chang CH; Immunology Graduate Program, University of Michigan Medical School, Ann Arbor, MI.; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2023 Mar 01; Vol. 7 (3), pp. 235-242.
DOI:	10.4049/immunohorizons.2300002
Abstrakt:	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. (Copyright © 2023 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu