Programmed cell death 5 transgenic mice attenuates adjuvant induced arthritis by 2 modifying the T lymphocytes balance

Feng Yuan,Zhao Li,Keshi Zhang,Zhenpeng Guan,Junfeng Wang

doi:10.1186/s40659-017-0145-4

Abstract

BackgroundProgrammed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The effects and mechanisms exerted by key mediators of arthritic inflammation remain unclear in PDCD5 transgenic (PDCD5 tg) mice.ResultsIn the current study, PDCD5 tg mice inhibited the progression of adjuvant-induced arthritis, specifically decreasing clinical signs and histological damage, compared with arthritis control mice. Additionally, the ratio of CD4+IFN-γ+ cells (Th1) and CD4+IL-17A+ cells (Th17), as well as the mRNA expression of the pro-inflammatory mediators IFN-γ, IL-6, IL-17A and TNF-α, were decreased in PDCD5 tg mice, while CD4+CD25+Foxp3+ regulatory T (Treg) cells and the anti-inflammatory mediators IL-4 and IL-10 were increased. Furthermore, PDCD5 tg mice demonstrated reduced serum levels of IFN-γ, IL-6, IL-17A and TNF-α and increased levels of IL-4.ConclusionsBased on our data, PDCD5 exerts anti-inflammatory effects by modifying the T lymphocytes balance, inhibiting the production of pro-inflammatory mediators and promoting the secretion of anti-inflammatory cytokines, validating PDCD5 protein as a possible treatment for RA.

Highlights

Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation
PDCD5 tg mice attenuates the development of Adjuvant-induced arthritis (AIA) and protects the joint against inflammatory destruction To validate the anti-inflammatory effects of PDCD5 on AIA mice, clinical signs and pathological changes were first observed to evaluate arthritis severity
PDCD5 tg mice increases Treg proportion and decreases the Th1 and Th17 ratio Because the relationships between T lymphocytes are disturbed during the pathological processes in AIA, we studied the percentages of Treg, Th1 and Th17 among splenocytes using flow cytometry

Summary

Introduction

Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The aetiology and pathogenesis of RA have not been confirmed, immune factors, T lymphocyte-mediated autoimmune responses, are involved in disease progression [2]. PDCD5 is an apoptosis-related gene cloned from TF-1 cells that is evolutionarily conserved and widely expressed in vivo [5]. The molecular mechanism by which PDCD5 accelerates cell apoptosis primarily involves the Tip60-p53 signalling pathway [6]. Restoration of normal levels of PDCD5 in vivo can enhance the sensitivity of various tumour cells to chemotherapeutic drugs by inducing apoptosis [7,8,9]. Growing numbers of researchers have focused on another important biological function of PDCD5: immune regulation. In our preliminary studies, PDCD5 levels in plasma and synovial fluid were

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