Sakkas Lazaros I, Mavropoulos Athanasios, Zafiriou Efterpi, Roussaki-Schulze Aggeliki, Bogdanos Dimitrios P
Department of Rheumatology and Clinical Immunology and.
Dermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
Mediterr J Rheumatol. 2018 Mar 19;29(1):59-61. doi: 10.31138/mjr.29.1.59. eCollection 2018 Mar.
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.
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.
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.
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.
This study will elucidate the molecular pathways of Apremilast and better define Bregs in PsA and Ps.
产生白细胞介素-10的调节性B细胞（Bregs）在自身免疫中具有重要意义，因为它们可抑制促炎性T细胞。我们已经表明，银屑病关节炎（PsA）中产生白细胞介素-10的Bregs减少，且与干扰素γ+T细胞（TH1细胞）和白细胞介素-17+T细胞（TH17细胞）呈负相关。过表达CD39的B细胞对促炎性T细胞也有抑制作用。
我们的初步数据显示，用于治疗PsA和银屑病（Ps）的磷酸二酯酶-4（PDE-4）抑制剂阿普司特可增加产生白细胞介素-10的Bregs，并减少干扰素γ+CD3+T细胞和白细胞介素-17+CD3+T细胞。我们还发现，PsA中p38丝裂原活化蛋白激酶和转录因子信号转导及转录激活因子3（STAT3）这两条白细胞介素-10产生的重要信号通路的激活减少。
本研究计划的目的是首次研究阿普司特对PsA和Ps患者外周血单个核细胞（PBMCs）和CD39高表达B细胞信号通路的免疫调节作用。
我们将研究PsA和Ps患者在阿普司特治疗前后B细胞中CD39的表达及其与干扰素γ+和白细胞介素-17+T细胞的关系。研究PsA和Ps患者在阿普司特治疗前后PBMCs和CD39高表达B细胞中cAMP反应元件结合蛋白（CREB）、STAT3和p38丝裂原活化蛋白激酶的激活情况。还将研究CD39高表达B细胞对T细胞干扰素γ和白细胞介素-17产生的影响。
本研究将阐明阿普司特的分子途径，并更好地界定PsA和Ps中的Bregs。
