SummaryThe role of naturally occurring regulatory T cells (Treg), known to be phenotypically heterogeneous, in controlling the expression of systemic lupus erythematosus (SLE) is incompletely defined. Therefore, different subpopulations of CD4 + FoxP3 + Tregs in patients with active or inactive SLE were investigated and compared with those of healthy subjects and patients with ankylosing spondylitis (AS). Characterization of different subsets of circulating CD4 + FoxP3 + Tregs was examined using flow cytometry. CD4 + CD25 high T cells were sorted and examined for suppressive activity in vitro. The results showed first that a significant decrease in the frequency of CD4 + CD25 high FoxP3 + T cells was present in patients with active SLE (n = 58), compared with healthy controls (n = 36) and AS patients (n = 23). In contrast, the frequencies of CD25 low FoxP3 + and CD25 ) FoxP3 + CD4 + T cells were significantly increased in patients with active SLE by comparison with the control subjects. The elevation of these two putative Treg subpopulations was associated with lower plasma levels of complement C3 and C4 in patients with SLE. In addition, the ratios of the three subsets of CD4 + FoxP3 + Tregs versus effector T cells (CD4 + CD25 + FoxP3 ) ) were inversely correlated with the titer of antidouble-stranded DNA IgG in patients with inactive, but not active, SLE. These results suggest that the pathogenesis of SLE may be associated with a defect in the homeostatic control of different Treg subsets.

It has been documented that sex hormone may play a role in the pathogenesis of murine lupus. To determine the effect of tamoxifen (TAM) on NZB/W F1 female mice, a total dose of 800 mg (22 mg/kg body weight) of TAM was administered subcutaneously every 2 weeks. The control mice were injected with peanut oil only. After treatment with TAM for 5 months, the mice were killed and immunological parameters were evaluated. The results suggest that NZB/W F1 mice treated with TAM had less severe proteinuria and increased survival rate compared to controls. Flow cytometric analysis of splenocytes revealed a signi®cantly lower percentage of B cells and CD5 B cells in the TAM-treated group. There was a signi®cantly lower serum level of soluble tumour necrosis factor (TNF) receptor I and II molecules in the TAM-treated mice. Immunohistological study showed that control mice had severe immune complex deposition in the kidney. In contrast, TAM-treated mice had much less pathological change. In summary, this study demonstrated that TAM treatment might be able to alleviate the symptoms of lupus nephritis, in¯uence B-cell count, modulate the expression of cytokine receptors and thereby subsequently affect immune function. Further studies to determine the cellular mechanisms in lupus nephritis may increase our understanding of this complex disease and provide additional targets for therapeutic intervention.

Chronic inflammation drives initiation of hepatocellular carcinoma (HCC), but the underlying mechanisms linking inflammation and tumor formation remain obscure. In this study, we compared the expression of interleukin (IL)-6 and cyclin D1 (CCND1) with the IL-6-induced homeobox gene ISX (intestine-specific homeobox) in 119 paired specimens of HCCs and adjacent normal tissues and also in paired specimens from 11 patients with non-HCCs. In pathologic analysis, ISX exhibited a tumor-specific expression pattern and a high correlation to patient survival time, tumor size, tumor number, and progression stage. Enforced expression of ISX accelerated cell proliferation and tumorigenic activity in hepatoma cells through CCND1 induction. In contrast, short hairpin RNA-mediated attenuation of ISX in hepatoma cells decreased cell proliferation and malignant transformation in vitro and in vivo. A high positive correlation existed in human hepatoma tumors between ISX and CCND1 expression. Together, our results highlight ISX as an important regulator in hepatoma progression with significant potential as a prognostic and therapeutic target in HCCs. Cancer Res; 73(2); 508-18. Ó2012 AACR.