The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis

Lazaros I Sakkas; Athanasios Mavropoulos; Efterpi Zafiriou; Aggeliki Roussaki-Schulze; Dimitrios P Bogdanos

doi:10.31138/mjr.29.1.59

The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis

Mediterr J Rheumatol. 2018 Mar 19;29(1):59-61. doi: 10.31138/mjr.29.1.59. eCollection 2018 Mar.

Authors

Lazaros I Sakkas¹, Athanasios Mavropoulos¹, Efterpi Zafiriou², Aggeliki Roussaki-Schulze², Dimitrios P Bogdanos¹

Affiliations

¹ Department of Rheumatology and Clinical Immunology and.
² Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Abstract

Background: IL-10-producing regulatory B cells (Bregs) are of great importance in autoimmunity, as they inhibit proinflammatory T cells. We have shown that IL-10-producing Bregs in psoriatic arthritis(PsA) were decreased and inversely correlated with IFNγ+T cells (TH1 cells) and IL-17+ T cells (TH17 cells). B cells with overexpression of CD39 have also inhibitory effects on proinflammatory T cells.

Preliminary results: Our preliminary data showed that Apremilast, a phosphodiesterase-4(PDE-4) inhibitor, used in the treatment of PsA and psoriasis (Ps) increased IL-10-producing Bregs and reduced IFNγ+CD3+ T cells and IL-17+CD3+ T cells. We also found reduced activation of p38MAP kinase and the transcription factor STAT3, two important signaling pathways of IL-10 production, in PsA.

Specific aims: The aim of this research proposal is to study for the first time the immunomodulatory effect of Apremilast on signaling pathways in peripheral blood mononuclear cells (PBMCs) and CD39high B cells in PsA and Ps.

Methods: We will study CD39 expression in B cells from patients with PsA and Ps before and after Apremilast treatment and their relation to IFNγ+ and IL-17+ T cells. Activation of CREB (cAMP response element-binding protein), STAT3, and p38MAPK in PBMCs and CD39high B cells from patients with PsA and Ps before and after Apremilast. The effect of CD39high B cells on T cell IFNγ and IL-17 production will also be studied.

Significance: This study will elucidate the molecular pathways of Apremilast and better define Bregs in PsA and Ps.

Keywords: Apremilast; CD39; T cells; psoriasis; psoriatic arthritis; regulatory B cells.