02109nas a2200265   4500000000100000000000100001008004100002260001500043653001800058653002900076100002300105700002500128700001600153700001800169700002200187700001600209700002100225700001800246245015300264856005500417300001000472490000600482520134100488022001401829       2018                            d  c2018-07-0610aSkin diseases10aTranslational immunology1 aNicole K. Campbell1 aHannah K. Fitzgerald1 aAnna Malara1 aRoisin Hambly1 aCheryl M. Sweeney1 aBrian Kirby1 aJean M. Fletcher1 aAisling Dunne00aNaturally derived Heme-Oxygenase 1 inducers attenuate inflammatory responses in human dendritic cells and T cells: relevance for psoriasis treatment  uhttps://www.nature.com/articles/s41598-018-28488-6  a102870 v83 aPsoriasis is a chronic autoimmune disease mediated by dysregulated immune responses in dendritic cells (DC) and T cells. The stress-response enzyme heme oxygenase-1 (HO-1) has been described as protective in animal models of psoriasis, however, implementation of HO-1-based therapies is hindered by the lack of clinically-suitable HO-1 inducers. The plant-derived polyphenols, carnosol and curcumin, have been identified as candidate HO-1 inducers however there has been little investigation into their effects on human immune cells. We demonstrate that treatment of human DC with these polyphenols limits DC maturation, reduces pro-inflammatory cytokine production, and prevents induction of allospecific T cell responses, in a manner partially dependent on carbon monoxide (CO). We also characterised their effects in ex-vivo psoriasis PBMC and report that curcumin, but not carnosol, strongly reduces T cell proliferation and cytokine poly-functionality, with reduced expression of psoriatic cytokines IFNγ, IL-17, GM-CSF and IL-22. This study therefore supports reports highlighting the therapeutic potential of curcumin in psoriasis by providing insight into its immunological effects on healthy human DC and psoriasis PBMC. We also demonstrate, for the first time, the anti-inflammatory effects of carnosol in human immune cells.  a2045-2322