PLoS ONE (Jan 2013)

Curcumin inhibits CD4(+) T cell activation, but augments CD69 expression and TGF-β1-mediated generation of regulatory T cells at late phase.

  • Girak Kim,
  • Mi Seon Jang,
  • Young Min Son,
  • Min Ji Seo,
  • Sang Yun Ji,
  • Seung Hyun Han,
  • In Duk Jung,
  • Yeong-Min Park,
  • Hyun Jung Jung,
  • Cheol-Heui Yun

DOI
https://doi.org/10.1371/journal.pone.0062300
Journal volume & issue
Vol. 8, no. 4
p. e62300

Abstract

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BACKGROUND: Curcumin is a promising candidate for a natural medicinal agent to treat chronic inflammatory diseases. Although CD4(+) T cells have been implicated in the pathogenesis of chronic inflammation, whether curcumin directly regulates CD4(+) T cells has not been definitively established. Here, we showed curcumin-mediated regulation of CD2/CD3/CD28-initiated CD4(+) T cell activation in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Primary human CD4(+) T cells were stimulated with anti-CD2/CD3/CD28 antibody-coated beads as an in vitro surrogate system for antigen presenting cell-T cell interaction and treated with curcumin. We found that curcumin suppresses CD2/CD3/CD28-initiated CD4(+) T cell activation by inhibiting cell proliferation, differentiation and cytokine production. On the other hand, curcumin attenuated the spontaneous decline of CD69 expression and indirectly increased expression of CCR7, L-selectin and Transforming growth factor-β1 (TGF-β1) at the late phase of CD2/CD3/CD28-initiated T cell activation. Curcumin-mediated up-regulation of CD69 at late phase was associated with ERK1/2 signaling. Furthermore, TGF-β1 was involved in curcumin-mediated regulation of T cell activation and late-phase generation of regulatory T cells. CONCLUSIONS/SIGNIFICANCE: Curcumin not merely blocks, but regulates CD2/CD3/CD28-initiated CD4(+) T cell activation by augmenting CD69, CCR7, L-selectin and TGF-β1 expression followed by regulatory T cell generation. These results suggest that curcumin could directly reduce T cell-dependent inflammatory stress by modulating CD4(+) T cell activation at multiple levels.