PMID- 23100511 OWN - NLM STAT- MEDLINE DCOM- 20130118 LR - 20211021 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 189 IP - 11 DP - 2012 Dec 1 TI - ATP-binding cassette transporter G1 intrinsically regulates invariant NKT cell development. PG - 5129-38 LID - 10.4049/jimmunol.1201570 [doi] AB - 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 Vbeta7(+) iNKT cells, suggesting alterations in iNKT cell thymic selection. Furthermore, in response to CD3epsilon/CD28 stimulation, Abcg1(-/-) thymic iNKT cells showed reduced production of IL-4 but increased production of IFN-gamma. Our results demonstrate that changes in intracellular cholesterol homeostasis by ABCG1 profoundly impact iNKT cell development and function. FAU - Sag, Duygu AU - Sag D AD - Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. FAU - Wingender, Gerhard AU - Wingender G FAU - Nowyhed, Heba AU - Nowyhed H FAU - Wu, Runpei AU - Wu R FAU - Gebre, Abraham K AU - Gebre AK FAU - Parks, John S AU - Parks JS FAU - Kronenberg, Mitchell AU - Kronenberg M FAU - Hedrick, Catherine C AU - Hedrick CC LA - eng GR - R01 HL094525/HL/NHLBI NIH HHS/United States GR - R01 AI045053/AI/NIAID NIH HHS/United States GR - R01 AI4505/AI/NIAID NIH HHS/United States GR - R37 AI071922/AI/NIAID NIH HHS/United States GR - P01 HL055798/HL/NHLBI NIH HHS/United States GR - R01 HL097368/HL/NHLBI NIH HHS/United States GR - S10 RR027366/RR/NCRR NIH HHS/United States GR - R37 AI71922/AI/NIAID NIH HHS/United States GR - R01 HL085790/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20121024 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Antibodies) RN - 0 (CD28 Antigens) RN - 0 (CD3 Complex) RN - 0 (Lipoproteins) RN - 0 (Receptors, Antigen, T-Cell, alpha-beta) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/genetics/*immunology MH - Animals MH - Antibodies/pharmacology MH - Biological Transport/genetics/immunology MH - CD28 Antigens/agonists/immunology MH - CD3 Complex/immunology MH - Cell Differentiation/genetics/immunology MH - Cell Proliferation MH - Cholesterol/*immunology/metabolism MH - Gene Expression Regulation/*immunology MH - Interferon-gamma/biosynthesis/immunology MH - Interleukin-4/biosynthesis/immunology MH - Lipoproteins/genetics/*immunology MH - Membrane Microdomains/immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Natural Killer T-Cells/cytology/*immunology MH - Primary Cell Culture MH - Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology MH - *Signal Transduction MH - Thymus Gland PMC - PMC3776580 MID - NIHMS511813 EDAT- 2012/10/27 06:00 MHDA- 2013/01/19 06:00 PMCR- 2013/12/01 CRDT- 2012/10/27 06:00 PHST- 2012/10/27 06:00 [entrez] PHST- 2012/10/27 06:00 [pubmed] PHST- 2013/01/19 06:00 [medline] PHST- 2013/12/01 00:00 [pmc-release] AID - jimmunol.1201570 [pii] AID - 10.4049/jimmunol.1201570 [doi] PST - ppublish SO - J Immunol. 2012 Dec 1;189(11):5129-38. doi: 10.4049/jimmunol.1201570. Epub 2012 Oct 24.