Role of dendritic cell maturation factors produced by human invariant NKT cells in immune tolerance.
In this study, we used the culture supernatant of iNKT cells to identify human myeloid DC maturation factors produced by human CD4+iNKT cells. S100A8 had a strong maturation effect. Notably, the recombinant S100A8 protein displayed properties of DC maturation functioning, and the induction of DC differentiation by both the purified and the recombinant protein were blocked by anti-S100A8 and anti-TLR-4 mAbs. DC differentiation induced by anti-major histocompatibility complex class II/CD1d Ab, S100A8, or both was qualitatively indistinguishable from that induced by the coculture of DCs and iNKT cells or via culture supplementation with supernatants from activated CD4+iNKT cells. S100A8 also induced CD4+/CD25+/Foxp3+Tregcells from naïve T cells. S100A8 may contribute to DC differentiation by elevating transcription factors or activating transcription factor-2, heat shock factor-1, or both, in mature DCs. S100A8 is a novel candidate iNKT cell-dependent DC maturation factor.
Departments of Tropical Medicine and Parasitology, Inha University School of Medicine, Incheon, Republic of Korea.|Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida.
Hyeong-Woo
HW
Lee
OncoMed Pharmaceuticals, Inc., Redwood City, California.
Hyun Bae
HB
Jie
Division of Infectious Diseases, Stanford University Medical Center, Stanford, California; and.
Paul L
PL
Bollyky
Thermo Fisher Scientific Biomarkers Research Initiatives in Mass Spectrometry (BRIMS) Center, Cambridge, Massachusetts.
David
D
Sarracino
Departments of Tropical Medicine and Parasitology, Inha University School of Medicine, Incheon, Republic of Korea; tongsookim@inha.ac.kr.
Tong-Soo
TS
Kim
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida; bwilson1@ufl.edu.
Brian S
BS
Wilson
D057134:Antibodies, Neutralizing / Q000494:pharmacology; D055610:Antigens, CD1d / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D008954:Models, Biological; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D009418:S100 Proteins / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D057134:Antibodies, Neutralizing; D055610:Antigens, CD1d; C526877:CD1D protein, human; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D009418:S100 Proteins; D051197:Toll-Like Receptor 4; D014157:Transcription Factors
ATF-2; CD4+ iNKT cells; HSF-1; TLR-4; regulatory T cell