Summary: Interleukin (IL)‐17 is a pro‐inflammatory cytokine produced by recently described T helper type 17 (Th17) cells, which have critical role in immunity to extracellular bacteria and the pathogenesis of several autoimmune disorders. IL‐6 and transforming growth factor (TGF)‐β are crucial for the generation of Th17 cells in mice, while the production of IL‐17 is supported by various cytokines, including IL‐23, IL‐1β, IL‐21, IL‐15 and tumour necrosis factor (TNF)‐α. In this study, the influence of a multifunctional cytokine, macrophage migration inhibitory factor (MIF), on IL‐17 production in mice was investigated. Treatment of lymph node cells (LNCs) with recombinant MIF up‐regulated mitogen‐stimulated IL‐17 expression and secretion. Additionally, LNCs from MIF knockout mice (mif^−/−) had severely impaired production of IL‐17, as well as of IL‐1β, IL‐6, IL‐23 and TGF‐β. When stimulated with recombinant IL‐1β, IL‐23 or TNF‐α, mitogen‐triggered mif^−/−LNCs were fully able to achieve the IL‐17 production seen in wild‐type (WT) LNCs, while the addition of IL‐6 and TGF‐β had no effect. Finally, after injection of mice with complete Freund’s adjuvant, secretion of IL‐17 as well as the number of IL‐17‐positive cells was significantly lower in the draining lymph nodes of mif^−/−mice in comparison with WT mice. The effect of MIF on IL‐17 production was dependent on p38, extracellular signal‐regulated kinase (ERK), Jun N‐terminal kinase (JNK) and Janus kinase 2/signal transducer and activator of transcription 3 (Jak2/STAT3), and not on nuclear factor (NF)‐κB and nuclear factor of activated T cells (NFAT) signalling. Bearing in mind the contribution of MIF and IL‐17 to the pathology of inflammatory and autoimmune disorders, from the results presented here it seems plausible that targeting MIF biological activity could be a valid therapeutic approach for the treatment of such diseases.

Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as a consequence of pancreatic β-cell destruction and results in hyperglycaemia. Since current T1D therapy mainly involves insulin replacement, the aim of the present study was to evaluate the therapeutic potential ofOriganum vulgareL. ssp.hirtum(Greek oregano) leaf extract rich in biophenols for the treatment of T1D. The phytochemical profile of methanolic oregano extract (MOE) and aqueous oregano extract (AOE) was determined by liquid chromatography/electrospray ion-trap tandem MS (LC/DAD/ESI-MSn), while their main compounds were quantified by HPLC with diode array detection. After establishing their potentin vitroantioxidant activity, the extracts were administered to C57BL/6 mice treated with multiple low doses of streptozotocin for diabetes induction. While prophylactic AOE therapy had no impact on diabetes induction, MOE reduced diabetes incidence and preserved normal insulin secretion. In addition, MOE scavenged reactive oxygen and nitrogen species and, therefore, alleviated the need for the up-regulation of antioxidant enzymes. MOE treatment specifically attenuated the pro-inflammatory response mediated by T helper 17 cells and enhanced anti-inflammatory T helper 2 and T regulatory cells through the impact on specific signalling pathways and transcription factors. Importantly, MOE preserved β-cells fromin vitroapoptosis via blockade of caspase 3. Finally, rosmarinic acid, a predominant compound in MOE, exhibited only partial protection from diabetes induction. In conclusion, acting as an antioxidant, immunomodulator and in an anti-apoptotic manner, MOE protected mice from diabetes development. Seemingly, there is more than one compound responsible for the beneficial effect of MOE.