Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine-protective regulatory T cells.
The gut is home to a large number of Treg, with both CD4(+) CD25(+) Treg and bacterial antigen-specific Tr1 cells present in normal mouse intestinal lamina propria. It has been shown recently that intestinal mucosal DC are able to induce Foxp3(+) Treg through production of TGF-beta plus retinoic acid (RA). However, the factors instructing DC toward this mucosal phenotype are currently unknown. Curcumin has been shown to possess a number of biologic activities including the inhibition of NF-kappaB signaling. We asked whether curcumin could modulate DC to be tolerogenic whose function could mimic mucosal DC. We report here that curcumin modulated BM-derived DC to express ALDH1a and IL-10. These curcumin-treated DC induced differentiation of naïve CD4(+) T cells into Treg resembling Treg in the intestine, including both CD4(+)CD25(+) Foxp3(+) Treg and IL-10-producing Tr1 cells. Such Treg induction required IL-10, TGF-beta and retinoic acid produced by curcumin-modulated DC. Cell contact as well as IL-10 and TGF-beta production were involved in the function of such induced Treg. More importantly, these Treg inhibited antigen-specific T-cell activation in vitro and inhibited colitis due to antigen-specific pathogenic T cells in vivo.
Cong
Yingzi
Y
Division of Gastroenterology and Hepatology, Department of Medicine, Birmingham, AL 35294-0007, USA. ycong@uab.edu
Wang
Lanfang
L
Konrad
Astrid
A
Schoeb
Trenton
T
Elson
Charles O
CO
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002469:Cell Separation; D003092:Colitis / Q000276:immunology; D003474:Curcumin / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000187:drug effects*; D018928:Immunity, Mucosal / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D056747:Immunomodulation / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D007422:Intestines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D007155:Immunologic Factors; D003474:Curcumin