PMID- 18445008 OWN - NLM STAT- MEDLINE DCOM- 20090220 LR - 20211020 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 125 IP - 3 DP - 2008 Nov TI - Serum lipids regulate dendritic cell CD1 expression and function. PG - 289-301 LID - 10.1111/j.1365-2567.2008.02842.x [doi] AB - Dendritic cells (DCs) are highly potent antigen-presenting cells (APCs) and play a vital role in stimulating naive T cells. Treatment of human blood monocytes with the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 stimulates them to develop into immature dendritic cells (iDCs) in vitro. DCs generated by this pathway have a high capacity to prime and activate resting T cells and prominently express CD1 antigen-presenting molecules on the cell surface. The presence of human serum during the differentiation of iDCs from monocytes inhibits the expression of CD1a, CD1b and CD1c, but not CD1d. Correspondingly, T cells that are restricted by CD1c showed poor responses to DCs that were generated in the presence of human serum, while the responses of CD1d-restricted T cells were enhanced. We chemically fractionated human serum to isolate the bioactive factors that modulate surface expression of CD1 proteins during monocyte to DC differentiation. The human serum components that affected CD1 expression partitioned with polar organic soluble fractions. Lysophosphatidic acid and cardiolipin were identified as lipids present in normal human serum that potently modulate CD1 expression. Control of CD1 expression was mediated at the level of gene transcription and correlated with activation of the peroxisome proliferator-activated receptor (PPAR) nuclear hormone receptors. These findings indicate that the ability of human DCs to present lipid antigens to T cells through expression of CD1 molecules is sensitively regulated by lysophosphatidic acid and cardiolipin in serum, which are ligands that can activate PPAR transcription factors. FAU - Leslie, David S AU - Leslie DS AD - Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Dascher, Christopher C AU - Dascher CC FAU - Cembrola, Katherine AU - Cembrola K FAU - Townes, Maria A AU - Townes MA FAU - Hava, David L AU - Hava DL FAU - Hugendubler, Lynne C AU - Hugendubler LC FAU - Mueller, Elisabetta AU - Mueller E FAU - Fox, Lisa AU - Fox L FAU - Roura-Mir, Carme AU - Roura-Mir C FAU - Moody, D Branch AU - Moody DB FAU - Vincent, Michael S AU - Vincent MS FAU - Gumperz, Jenny E AU - Gumperz JE FAU - Illarionov, Petr A AU - Illarionov PA FAU - Besra, Gurdyal S AU - Besra GS FAU - Reynolds, Carol G AU - Reynolds CG FAU - Brenner, Michael B AU - Brenner MB LA - eng GR - G0400421/MRC_/Medical Research Council/United Kingdom GR - G9901077/MRC_/Medical Research Council/United Kingdom GR - R01 HL071590/HL/NHLBI NIH HHS/United States GR - R01 AI049313/AI/NIAID NIH HHS/United States GR - K08 AR002171/AR/NIAMS NIH HHS/United States GR - K08AR02171/AR/NIAMS NIH HHS/United States GR - 07221/Z/03/Z/WT_/Wellcome Trust/United Kingdom GR - R56 AI074940/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080428 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Antigens, CD1) RN - 0 (Lipids) RN - 0 (Peroxisome Proliferator-Activated Receptors) SB - IM MH - Antigen Presentation/immunology MH - Antigens, CD1/*metabolism MH - Cell Differentiation/immunology MH - Cells, Cultured MH - Coculture Techniques MH - Dendritic Cells/*immunology MH - Gene Expression MH - Humans MH - Lipids/*immunology MH - Lymphocyte Activation/immunology MH - Peroxisome Proliferator-Activated Receptors/biosynthesis/genetics/immunology MH - Serum/immunology MH - T-Lymphocyte Subsets/immunology PMC - PMC2669133 EDAT- 2008/05/01 09:00 MHDA- 2009/02/21 09:00 PMCR- 2009/11/01 CRDT- 2008/05/01 09:00 PHST- 2008/05/01 09:00 [pubmed] PHST- 2009/02/21 09:00 [medline] PHST- 2008/05/01 09:00 [entrez] PHST- 2009/11/01 00:00 [pmc-release] AID - IMM2842 [pii] AID - 10.1111/j.1365-2567.2008.02842.x [doi] PST - ppublish SO - Immunology. 2008 Nov;125(3):289-301. doi: 10.1111/j.1365-2567.2008.02842.x. Epub 2008 Apr 28.