Curcumin induces maturation-arrested dendritic cells that expand regulatory T cellsin vitroandin vivo

Abstract

SummaryDendritic cells (DC) and regulatory T cells (Tregs) are vital to the development of transplant tolerance. Curcumin is a novel biological agent extracted from Curcuma longa (turmeric), with anti-inflammatory and anti-oxidant activity mediated via nuclear factor (NF)-kB inhibition. We investigated the immunomodulatory effects of curcumin on human monocyte-derived and murine DC. Human monocyte-derived DC (hu-Mo-DC) were generated in the presence (CurcDC) or absence (matDC) of 25 mM curcumin, and matured using lipopolysaccharide (1 mg/ml). DC phenotype and allostimulatory capacity was assessed. CD11c+ DC were isolated from C57BL/6 mice, pretreated with curcumin and injected into BALB/c mice, followed by evaluation of in vivo T cell populations and alloproliferative response. Curcumin induced DC differentiation towards maturation-arrest. CurcDC demonstrated minimal CD83 expression (<2%), down-regulation of CD80 and CD86 (50% and 30%, respectively) and reduction (10%) in both major histocompatibility complex (MHC) class II and CD40 expression compared to matDC. CurcDC also displayed decreased RelB and interleukin (IL)-12 mRNA and protein expression. Functionally, CurcDC allostimulatory capacity was decreased by up to 60% (P < 0·001) and intracellular interferon (IFN-g) expression in the responding T cell population were reduced by 50% (P < 0·05). T cell hyporesponsiveness was due to generation of CD4 + CD25 hi CD127 lo forkhead box P3 (FoxP3) + Tregs that exerted suppressive functions on naïve syngeneic T cells, although the effect was not antigen-specific. In mice, in vivo infusion of allogeneic CurcDC promoted development of FoxP3 + Tregs and reduced subsequent alloproliferative capacity. Curcumin arrests maturation of DC and induces a tolerogenic phenotype that subsequently promotes functional FoxP3 + Tregs in vitro and in vivo.

Plant Components for Immune Modulation Targeting Dendritic Cells: Implication for Therapy

“…The expression of negative regulatory molecules PD-L1 and PD-L2 were also downregulated. IL-12p40 mRNA expression and biologically active IL-12 secretion by CurcDC were significantly reduced, while they could produce IL-10 as before [84]. These data are consistent with the observed suppression of NF-κB nuclear activity by curcumin [35,38].…”

“…These data are consistent with the observed suppression of NF-κB nuclear activity by curcumin [35,38]. The allostimulatory activity of CurDC and IFN-γ production in the responding T cells was reduced [84]. It can be concluded that CurcDC promotes FoxP3 + Tregs capable of inducing regulatory function on naive T cells.…”

Administration of Curcumin Protects Kidney Tubules Against Renal Ischemia-Reperfusion Injury (RIRI) by Modulating Nitric Oxide (NO) Signaling Pathway

“…Curcumin has immunomodulatory, anti-proliferative, antimicrobial, anti-inflammatory and antioxidant effects and hence has potential therapeutic value in IRI. Curcumin is insoluble in water with a high level of octanol: water partition coefficient (logPow= 3.29), which limits its application as an orally delivered agent [4-7]. Earlier studies determining the effectiveness of curcumin on IR injury in animal models have used oral delivery with slight functional salvage [8-10].…”

Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease

“…187,188 Curcumin treatment of LPS-matured DC arrests their maturation into a tolerogenic phenotype that preferentially promotes the suppressive function of T reg cells. 189 Oral treatment with curcumin alleviates intestinal inflammation by inhibiting proinflammatory Th1 cytokines. 183 However, curcumin has never been investigated in ocular inflammation.…”