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Delphinidin diminishes in vitro interferon-γ and interleukin-17 producing cells in patients with psoriatic disease

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Abstract

The anthocyanidin delphinidin reduces psoriasiform lesions and inflammatory mediators in human cell culture systems. Its role in psoriatic disease has not yet been investigated. We assessed delphinidin’s in vitro immunomodulatory effect on ex vivo stimulated peripheral blood mononuclear cells (PBMCs) from 50 individuals [26 with psoriasis, 10 with psoriatic arthritis (PsA) and 14 healthy controls (HCs)]. Cells were either left untreated or stimulated with PMA plus ionomycin in the presence or absence of delphinidin. Intracellular production of interferon-γ (IFNγ), interleukin-17A (IL-17A), and interleukin-10 (IL-10) was measured flow cytometrically. Delphinidin dose-dependently reduced IFNγ+ T cells from patients and HCs. The mean IFNγ decrease in CD4+ T subpopulations was 42.5 ± 28% for psoriasis patients, 51.8 ± 21.5% for PsA patients and 49 ± 17% for HCs (p < 0.001 for all). Similarly, IFNγ reduction in CD8+ T cells was 34 ± 21.6% for psoriasis patients, 47.1 ± 22.8% for PsA and 44.8 ± 14.3% for HCs (P < 0.001 for all). An inhibitory effect of delphinidin was also noted in IFNγ producing NKs and NKTs from psoriasis individuals. Delphinidin also significantly decreased IL-17+ CD4+ T cells in all tested subjects, with marginal effect on the increase of IL-10-producing T regulatory subsets. In conclusion, delphinidin exerts a profound in vitro anti-inflammatory effect in psoriasis and psoriatic arthritis by inhibiting IFNγ+ innate and adaptive cells and T helper (Th) 17 cells. If this effect is also exerted in vivo, delphinidin may be regarded as a nutraceutical with immunosuppressive potential.

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Acknowledgements

We would like to thank Prof Eirini Rigopoulou for critical reading of the manuscript and those participating in the study, patients as well as healthy controls.

Funding

This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Development of a predictive response algorithm in patients with psoriasis and psoriatic arthritis based on clinical, serological, immunological, and genetic biomarkers” (MIS 5048946).

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  1. Sotirios G. Tsiogkas and Αthanasios Mavropoulos contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

    Sotirios G. Tsiogkas, Αthanasios Mavropoulos, Dimitrios N. Skyvalidas, Eleni Patrikiou, Athina Ioanna Daponte, Maria G. Grammatikopoulou, Lazaros I. Sakkas & Dimitrios P. Bogdanos

  2. Department of Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

    Niki Ntavari, Aggeliki-Victoria Roussaki-Schulze & Efterpi Zafiriou

  3. Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

    Efthimios Dardiotis

  4. Department of Nutritional Sciences and Dietetics, Faculty of Health Sciences, International Hellenic University, Alexander Campus, Thessaloniki, Greece

    Maria G. Grammatikopoulou

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  1. Sotirios G. Tsiogkas
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Correspondence to Dimitrios P. Bogdanos.

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This study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board/Ethics committee of the university General Hospital of Larissa, University of Thessaly ECA #19/14–11-2019.

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12026_2021_9251_MOESM1_ESM.pdf

Supplementary file1. Representative gating strategy of lymphocytes in untreated, PMA/ionomycin and PMA/ionomycin/delphinidin treated cells. Cell viability was maintained and equal percentages of lymphocytes were gated in all experimental conditions. (PDF 485 KB)

12026_2021_9251_MOESM2_ESM.pdf

Supplementary file2. Representative gating strategy in untreated, PMA/ionomycin and PMA/ionomycin/delphinidin treated cells. Individual cell subsets were sub-gated according to the expression of CD3, CD4, CD8 and CD56 surface markers. All surface epitopes were sufficiently maintained and detected following cell activation with PMA/ionomycin in the presence of delphinidin. (PDF 288 KB)

12026_2021_9251_MOESM3_ESM.pdf

Supplementary file3. Representative flow cytometric analysis of IL-10 producing CD4+ T cells and CD4+CD25hi Tregs following delphinidin pre-treatment and LPS activation of PBMCs from a psoriasis patient naïve to biological therapy. (PDF 267 KB)

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Tsiogkas, S.G., Mavropoulos, Α., Skyvalidas, D.N. et al. Delphinidin diminishes in vitro interferon-γ and interleukin-17 producing cells in patients with psoriatic disease. Immunol Res 70, 161–173 (2022). https://doi.org/10.1007/s12026-021-09251-y

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