Adiponectin inhibits oxidization-induced differentiation of T helper cells through inhibiting costimulatory CD40 and CD80

Abstract

Adiponectin is a multifunctional adipokine that has several oligomeric forms in the blood stream, which broadly regulates innate and acquired immunity. Therefore, in this study, we aimed to observe the differentiation of T helper (Th) cells and expression of costimulatory signaling molecules affected by adiponectin. The mRNA and protein expression levels of adiponectin and its receptors in oxidized low density lipoprotein cholesterol-treated endothelial cells were assayed by real time PCR and immunofluorescence. The endothelial cells were then treated with adiponectin with or without adipoR1 or adipoR2 siRNA and co-cultured with T lymphocytes. The distribution of Th1, Th2 and Th17 subsets were assayed by flow cytometry. The effects of adiponectin on costimulatory signaling molecules HLA-DR, CD80, CD86 and CD 40 was also assayed by flow cytometry. The results showed that endothelial cells expressed adiponectin and its receptor adipoR1 and adipoR2, but not T-cadherin. Adiponectin suppressed Th1 and Th17 differentiation through adipoR1 receptor, contributed to the inhibition of CD80 and CD40, and inhibited differentiation of Th1 and Th17 by inhibiting antigen presenting action.

The Role of Adipokines in the Pathogenesis of Psoriasis

“…Furthermore, Surendar and colleagues found that the stimulation of naïve CD4+ cells with adiponectin leads to a reduced number of IFN-γ+ T cells [ 83 ]. Similarly, a separate study showed that adiponectin suppresses the ox-LDL-induced differentiation of Th1 and Th17 cells [ 84 ]. Additionally, in line with previous studies, Zhang et al found that adiponectin suppressed the Th1 and Th17 cytokines IFN-γ and IL-6, respectively [ 85 ].…”

The role of adipokines in the modulation of lymphoid lineage cell development and activity: An overview

“…It has been demonstrated that adiponectin markedly increases T-box transcription factor T-bet 115 and ROR-γt 116 expression in CD4 + T cells indicating that this adipokine enhances the differentiation to Th1 and Th17 phenotype, respectively. On the other hand, Xiao et al 117 suggested that adiponectin may suppress the differentiation of Th1 and Th17 from CD4 + T lymphocytes through inhibition of costimulatory molecules involved in this process, that is, CD80 and CD40. These observations were further confirmed by Zhang et al 118 who demonstrated that treatment of CD4 + T cells with adiponectin inhibited the differentiation to Th1…”

The role of adiponectin for immune cell function in metabolic diseases

“…In particular, exogenous adiponectin inhibited IFN‐γ during Th1 cell differentiation and downregulated the Th17 cytokines during Th17 cell differentiation, which was mediated through the SIRT1‐PPARγ‐RORγt pathway 78 . Moreover, adiponectin was found to inhibit the differentiation of Th1 and Th17 cells through AdipoR1, resulting in the downregulation of CD80 and CD40, and suppressing antigen presentation to inhibit the differentiation of Th1 and Th17 cells in vitro 79 …”

“…78 Moreover, adiponectin was found to inhibit the differentiation of Th1 and Th17 cells through AdipoR1, resulting in the downregulation of CD80 and CD40, and suppressing antigen presentation to inhibit the differentiation of Th1 and Th17 cells in vitro. 79 Tregs that exert anti-inflammatory effects are severely reduced in fatty tissue in obese and IR states. New evidence indicates that g-APN impacts the capacity of Tregs to produce IL-10 and induces the expression of Forkhead box P3 (FOXP3).…”