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The systemic dysregulation of adaptive and innate immunity have been identified as major hallmark of systemic lupus erythematosus (SLE) pathogenesis that predominantly affects women. Patients with SLE develop heterogeneous clinical manifestations which involve of multiple organ damage including renal, spleen, nervous system, joints and hematopoietic organs. A high rate of cell death, e.g., NETosis, and clearance deficiencies by myeloid cells led to increased cell debris and accumulation of endogenous nucleic acids, and the presence of anti-nuclear antibodies (ANAs) derived from immune response can break of self-tolerance and exacerbate SLE pathology. Currently, the nucleic acid receptors, such as Toll-like receptors, RIG-I-like receptors, AIM2-like receptors and IFI 200-family have been uncovered to be potential predisposing causes for SLE via triggering interferon (IFN) response and maturation of IL-1β. Notably, as the newly found DNA sensor, cyclic GMP-AMP synthase (cGAS) can activate the stimulator of interferon genes (STING), which plays a pivotal role in DNA/RNA sensing pathway, for type I IFN and other inflammatory cytokines induction including IL-6 and attributes to STING-associated inflammatory disorders. Interestingly, the elevated levels of IFN-α/β and IFN-stimulated genes were found in SLE patients than healthy individuals. Given this, we propose a hypothesis that the cGAS-STING pathway in multiple organs function versatile and can facilitate overall disease progression of SLE though impertinent cytosolic self-DNA sensing. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the expression and function of toll-like receptor 3 (TLR3) in oral squamous cell carcinoma (OSCC). Study Design: We first assessed TLR3 expression in 20 cases of primary OSCC tissue. Two OSCC cell lines, SCC4 and CAL27, were used for further study. Lyophilized polyinosinic-polycytidylic acid [Poly(I:C)] was used to activate TLR3 expressed by OSCC. Changes in cytokines expression, cell viability, apoptosis, and migration in OSCC were investigated. Results: TLR3 was present in both OSCC tissue and the 2 OSCC cell lines examined. Poly(I:C) stimulated robust responses in OSCC: it upregulated cytokine expression; decreased cell viability by suppressing cell proliferation and inducing apoptosis; and decreased cell migration. Poly(I:C)-TLR3-induced OSCC cell apoptosis was caspase-3-dependent. Conclusions: The present study indicated that TLR3 might affect OSCC development and should be considered as a potential target for future OSCC immunotherapy. [Copyright &y& Elsevier]

Activity of nuclear factor κB transcription factors and signaling via signal transducer and activator of transcription (STAT) are frequently altered in gastric cancer cells. Mice lacking NFKB1 (Nfkb1 –/– mice) develop invasive gastric cancer, and their gastric tissues have increased levels of cytokines, such as interleukin (IL) 6, IL22, IL11, and tumor necrosis factor (TNF), as well as increased activation of STAT1. We investigated whether these cytokines were required for STAT1 activation in gastric tissues of mice and critical for gastric tumorigenesis. We crossed Nfkb1 –/– mice with Il6 –/–, Il22 –/– , Il11Rα –/– , and Tnf –/– mice. Stomach tissues from compound mutant mice were analyzed by histology, immunoblotting, and RNA sequencing. Lymphoid, myeloid, and epithelial cells were isolated from stomachs, and the levels of cytokines were determined by flow cytometric analysis. Nfkb1 –/– mice developed gastritis, oxyntic atrophy, gastric dysplasia, and invasive tumors, whereas Nfkb1 –/– Stat1 –/– mice did not, even when followed for as long as 2 years. The levels of Il6 , Il11 , Il22 , and Tnf messenger RNA were increased in the body and antrum of the stomachs from Nfkb1 –/– mice, from 3-6 months of age. However, Nfkb1 –/– Il6 –/– , Nfkb1 –/– Il22 –/– , and Nfkb1 –/– Il11Rα –/– mice still developed gastric tumors, although the absence of IL11 receptor (IL11R) significantly reduced development of invasive gastric tumors. Stomachs from Nfkb1 –/– Tnf –/– mice exhibited significantly less gastritis and oxyntic atrophy and fewer tumors than Nfkb1 –/– mice. This correlated with reduced activation of STAT1 and STAT3 and fewer numbers of T cells and B cells infiltrating the gastric body. Loss of STAT1 or TNF significantly reduced expression of PD-L1 on epithelial and myeloid (CD11b+) cells in the gastric mucosa of Nfkb1 –/– mice—indeed, to the levels observed on the corresponding cells from wild-type mice. In studies of gastric tumor development in knockout mice, we found that loss of NFKB1 causes increased expression of TNF in the stomach and thereby drives activation of STAT1, resulting in an inflammatory immune response and the development of gastric cancer. IL11R appears to be required for the progression of gastric tumors to the invasive stage. These findings suggest that inhibitors of TNF, and possibly also inhibitors of IL11/IL11Rα, might be useful in the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Previous studies showed that lectin galactoside-binding soluble 3 binding protein (LGALS3BP) is an important participant in tumor progression. However, its prognostic value and functional mechanism in oral squamous cell carcinoma (OSCC) are still unclear. In this study, we analyzed LGALS3BP expression in OSCC tissues via Oncomine databases and immunohistochemical staining. LGALS3BP was significantly up-regulated in OSCC tumor tissues. IHC analysis showed that LGALS3BP was predominantly expressed in tumor cells and correlated with poor clinical characteristics. In addition, high LGALS3BP expression predicted poor clinical outcomes and multivariate analysis revealed that LGALS3BP expression was as an independent prognostic factor for OS, DFS and RFS (p <.0001, p =.002, p =.002). Mechanically, LGALS3BP regulated OSCC proliferation and migration via PI3K/AKT pathways, which was abrogated by PI3K inhibitor LY294002 in a dose-dependent manner. Our results suggested that LGALS3BP could be served as a novel independent prognostic factor as well as a potential therapeutic target for OSCC treatment. Unlabelled Image • LGALS3BP is overexpressed in OSCC and correlated with poor clinical characteristics. • LGALS3BP is an independent prognostic factor for OS, DFS and RFS. • LGALS3BP promoted OSCC cell proliferation and migration via PI3K/AKT pathways. [ABSTRACT FROM AUTHOR]