The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis
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...
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PCO Convin S.A.
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doaj-8ca3429383b54b14ac828fa6c58345ef2020-11-25T00:52:36ZengPCO Convin S.A.Mediterranean Journal of Rheumatology2529-198X2018-01-01291596110.31138/mjr.29.1.59MJR-29-1-59The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritisLazaros I. Sakkas0Athanasios Mavropoulos1Efterpi Zafiriou2Aggeliki Roussaki-Schulze3Dimitrios P. Bogdanos4Department of 1Rheumatology and Clinical Immunology andDepartment of 1Rheumatology and Clinical Immunology andDermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDermatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, GreeceDepartment of 1Rheumatology and Clinical Immunology andBackground. 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.https://www.mjrheum.org/assets/files/792/file121_879.pdfapremilastcd39psoriatic arthritispsoriasisregulatory b cellst cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lazaros I. Sakkas Athanasios Mavropoulos Efterpi Zafiriou Aggeliki Roussaki-Schulze Dimitrios P. Bogdanos |
spellingShingle |
Lazaros I. Sakkas Athanasios Mavropoulos Efterpi Zafiriou Aggeliki Roussaki-Schulze Dimitrios P. Bogdanos The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis Mediterranean Journal of Rheumatology apremilast cd39 psoriatic arthritis psoriasis regulatory b cells t cells |
author_facet |
Lazaros I. Sakkas Athanasios Mavropoulos Efterpi Zafiriou Aggeliki Roussaki-Schulze Dimitrios P. Bogdanos |
author_sort |
Lazaros I. Sakkas |
title |
The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis |
title_short |
The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis |
title_full |
The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis |
title_fullStr |
The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis |
title_full_unstemmed |
The effect of Apremilast on signal transduction and IL-10 production in CD39high regulatory B cells in patients with psoriatic arthritis |
title_sort |
effect of apremilast on signal transduction and il-10 production in cd39high regulatory b cells in patients with psoriatic arthritis |
publisher |
PCO Convin S.A. |
series |
Mediterranean Journal of Rheumatology |
issn |
2529-198X |
publishDate |
2018-01-01 |
description |
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. |
topic |
apremilast cd39 psoriatic arthritis psoriasis regulatory b cells t cells |
url |
https://www.mjrheum.org/assets/files/792/file121_879.pdf |
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