ATP-binding cassette transporter G1 intrinsically regulates invariant NKT cell development

Duygu Sag, Gerhard Wingender, Heba Nowyhed, Runpei Wu, Abraham K. Gebre, John S. Parks, Mitchell Kronenberg, Catherine C. Hedrick

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


ATP-binding cassette transporter G1 (ABCG1) plays a role in the intracellular transport of cholesterol. Invariant NKT (iNKT) cells are a subpopulation of T lymphocytes that recognize glycolipid Ags. In this study, we demonstrate that ABCG1 regulates iNKT cell development and functions in a cell-intrinsic manner. Abcg1-/- mice displayed reduced frequencies of iNKT cells in thymus and periphery. Thymic iNKT cells deficient in ABCG1 had reduced membrane lipid raft content, and showed impaired proliferation and defective maturation during the early stages of development. Moreover, we found that Abcg1-/- mice possess a higher frequency of Vβ7+ iNKT cells, suggesting alterations in iNKT cell thymic selection. Furthermore, in response to CD3ε/CD28 stimulation, Abcg1-/- thymic iNKT cells showed reduced production of IL-4 but increased production of IFN-γ. Our results demonstrate that changes in intracellular cholesterol homeostasis by ABCG1 profoundly impact iNKT cell development and function.

Original languageEnglish (US)
Pages (from-to)5129-5138
Number of pages10
JournalJournal of Immunology
Issue number11
StatePublished - Dec 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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