Curdlan induces DC-mediated Th17 polarization via Jagged1 activation in human dendritic cells.
BACKGROUND
Th17-inducing activity is carried by certain polysaccharides such as beta-glucan derived from Candia albicans. Our previous studies have shown that Th1- and Th2-inducing activities can be qualitatively evaluated by the expression patterns of Notch ligand isoforms, using human monocyte-derived dendritic cells (Mo-DCs) and some leukemic cell lines such as THP-1. The association of Th17-inducing activities with Notch ligand expression patterns has been unclear.


METHODS
Mo-DCs from healthy volunteers were co-cultured with HLA-DR-nonshared allogeneic CD4+ naïve T cells to induce a mixed lymphocyte reaction, in the presence of adjuvants, such as curdlan. Culture supernatants were assayed for IFNgamma, IL-5 and IL-17 by an enzyme-linked immunosorbent assay (ELISA). Notch ligand expression on Mo-DCs and THP-1 cells was evaluated by using RT-PCR.


RESULTS
The present study shows that curdlan, one of the beta-glucans, has the ability to induce DC-mediated Th17 differentiation. It is also interesting to note that Jagged1 mRNA in Mo-DCs and THP-1 cells is up-regulated by curdlan. Furthermore, polyclonal anti-Jagged1 antibody inhibited such DC-mediated Th17 differentiation.


CONCLUSIONS
This study suggests that curdlan induces human DC-mediated Th17 polarization via Jagged1 activation in DCs.
Higashi
Takehiro
T
Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
Hashimoto
Kumiko
K
Takagi
Rie
R
Mizuno
Yosuke
Y
Okazaki
Yasushi
Y
Tanaka
Yoshiya
Y
Matsushita
Sho
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D019138:Antibodies, Blocking; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000473:pathology; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000494:pharmacology; D000072099:Serrate-Jagged Proteins; D015854:Up-Regulation; D047071:beta-Glucans / Q000276:immunology* / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D002135:Calcium-Binding Proteins; D006684:HLA-DR Antigens; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011135:Polysaccharides, Bacterial; D000072099:Serrate-Jagged Proteins; D047071:beta-Glucans; C038459:curdlan