A novel role for adiponectin in regulating the immune responses in chronic hepatitis C virus infection†‡

Abstract

Adipose tissue releases pro-inflammatory and anti-inflammatory mediators, including adiponectin, which elicit a broad range of metabolic and immunological effects. The study aim was to determine in subjects infected with chronic hepatitis C virus (HCV) the effects of total adiponectin and its high-molecular-weight (HMW) and low-molecular-weight isoforms on HCV-specific immune responses. Serum levels of total adiponectin and its isoforms were determined by immunoassay. The ex vivo effect of adiponectin on the HCV-specific T-cell response was examined by interferon gamma (IFN-␥) enzyme-linked immunosorbent spot and enzyme-linked immunosorbent assay cytokine assays. The role of the mitogen-activated protein kinase (MAPK) signaling pathway in mediating the adiponectin effect on T cells was also evaluated. We found that serum levels of total and HMW adiponectin were significantly decreased in subjects with chronic HCV and increased body mass index (BMI) compared with HCV-infected lean subjects. The presence of an anti-HCV specific immune response was strongly associated with lower BMI (P ‫؍‬ 0.004) and higher serum total (P ‫؍‬ 0.01) and HMW (P ‫؍‬ 0.02) adiponectin. In ex vivo assays, total adiponectin and the HMW adiponectin isoform enhanced HCV-specific IFN-␥ production (P ‫؍‬ 0.02 and 0.03, respectively). Adiponectin-R1 receptors were expressed on T cells and monocytes. In depletion experiments, the IFN-␥ response to adiponectin was entirely dependent on the simultaneous presence of both CD4 and CD8 T cells, and to a lesser extent, natural killer cells. Selective inhibition of p38MAPK activity by SB203580 abrogated the IFN-␥ response to adiponectin, whereas extracellular signal-regulated kinase 1/2 inhibition by PD98059 did not affect the response. Conclusion: In chronic HCV, a reciprocal association exists between BMI, adiponectin, and the anti-HCV immune responses, emphasizing the important role played by adiposity in regulating the immune response in HCV infection. (HEPATOLOGY 2008;48: 374-384.)

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

“…Quantitative real-time PCR detected both AdipoR1 and AdipoR2 mRNA in dermal gd-T cells, although AdipoR2 protein expression was below the detection limit by western blot analysis. This result is consistent with the past reports demonstrating discrepancy between mRNA and protein levels of AdipoR2 in leukocytes 41,42 . Control experiments have revealed that AdipoR1 and AdipoR2 mRNA levels are reduced by 465% as evaluated by real-time reverse transcription-PCR analysis (Fig.…”

Adiponectin Induces Pro-inflammatory Programs in Human Macrophages and CD4+ T Cells

“…Examination of the expression of the adiponectin receptors, AdipoR1 and AdipoR2, in these cells concurred with a previous report (37) showing that CD4 ϩ T cells express AdipoR1 preferentially (data not shown). To investigate the effects of adiponectin on purified CD4 ϩ T cells, we subjected these human cells to polyclonal stimulation in the presence or absence of adiponectin and examined the expression of IFN-␥ and IL-4, signature cytokines of the T H 1 and T H 2 lineages, respectively, and of the broad inflammatory mediator IL-6.…”

“…In contrast, adiponectin limits both T cell proliferation and apoptosis when added to human PBMCs together with a polyclonal T cell activator (36). Recent studies addressing the role of adiponectin on the expansion of antigen-specific T cell populations from human PBMCs have also yielded discordant results as follows: adiponectin reduced the number of influenza-specific T cells producing IFN-␥ and TNF-␣ (36) but increased IFN-␥ production by hepatitis C virus-specific T cells (37). These results indicate that the action of adiponectin on T cell differentiation and function varies among species and that the experimental conditions used in vitro (e.g.…”

Potential Role of Leptin, Adiponectin and Three Novel Adipokines—Visfatin, Chemerin and Vaspin—in Chronic Hepatitis

“…In the study by Palmer et al (145) high concentrations of total and high-molecular weight adiponectin were related to the presence of a cellular immune response against HCV, suggesting a pivotal role for adiponectin in the regulation of immunity in CHC. The study by Latif et al (146) showed that serum adiponectin levels inversely correlate not only with the grade of steatosis and histological activity index, but also with the stage of fibrosis (146).…”