Clinicopathological analysis of extraneural sporadic haemangioblastoma occurring in the tongue.

Haemangioblastoma is a morphologically distinctive tumour with uncertain histogenesis, typically occurring in the cerebellum, brain stem or spinal cord and less commonly in extraneural locations. Here, we present a case of haemangioblastoma occurring in the tongue, which is the first reported case in terms of the pathogenic site. The tumour was morphologically indistinguishable from central nervous system haemangioblastoma, that is, neoplastic stromal cells with cytoplasmic vacuolisation and abundant small vessels. Immunohistochemical studies revealed that the tumour cells were positive for S100, NSE, CD56, Syn, EMA, vimentin and α-inhibin, while negative for CK, SMA, factor Ⅷ, D2-40 and GFAP. Immunostainings for CD34 and CD31 outlined the rich and delicate vascular channels. Ki-67 expression was presented in approximately 3% of tumour cells. Primary haemangioblastoma has not been previously described at this site, and this case emphasises the need to consider haemangioblastoma in the differential diagnoses of neoplasms occurring in the tongue.

Aryl hydrocarbon receptor activation drives polymorphonuclear myeloid-derived suppressor cell response and efficiently attenuates experimental Sjögren's syndrome.

Myeloid-derived suppressor cells (MDSCs) comprise heterogeneous myeloid cell populations with immunosuppressive capacity that contribute to immune regulation and tolerance induction. We previously reported impaired MDSC function in patients with primary Sjögren's syndrome (pSS) and mice with experimental SS (ESS). However, the molecular mechanisms underlying MDSC dysfunction remain largely unclear. In this study, we first found that aryl hydrocarbon receptor (AhR) was highly expressed by human and murine polymorphonuclear MDSCs (PMN-MDSCs). Indole-3-propionic acid (IPA), a natural AhR ligand produced from dietary tryptophan, significantly promoted PMN-MDSC differentiation and suppressive function on CD4+ T cells. In contrast, feeding a tryptophan-free diet resulted in a decreased PMN-MDSC response, a phenotype that could be reversed by IPA supplementation. The functional importance of PMN-MDSCs was demonstrated in ESS mice by using a cell-depletion approach. Notably, AhR expression was reduced in PMN-MDSCs during ESS development, while AhR antagonism resulted in exacerbated ESS pathology and dysregulated T effector cells, which could be phenocopied by a tryptophan-free diet. Interferon regulatory factor 4 (IRF4), a repressive transcription factor, was upregulated in PMN-MDSCs during ESS progression. Chromatin immunoprecipitation analysis revealed that IRF4 could bind to the promoter region of AhR, while IRF4 deficiency markedly enhanced AhR-mediated PMN-MDSC responses. Furthermore, dietary supplementation with IPA markedly ameliorated salivary glandular pathology in ESS mice with restored MDSC immunosuppressive function. Together, our results identify a novel function of AhR in modulating the PMN-MDSC response and demonstrate the therapeutic potential of targeting AhR for the treatment of pSS.

Acteoside promotes B cell-derived IL-10 production and ameliorates autoimmunity.

IL-10-producing regulatory B (Breg) cells are well recognized for maintaining immune tolerance. The impaired Breg cell function with decreased IL-10-producing capacity has been found in autoimmune diseases, such as rheumatoid arthritis, lupus, and primary Sjogren's syndrome (pSS). However, seldom therapeutic agents targeting Breg cells are available to treat those autoimmune diseases. Here, we showed that acteoside (AC), a caffeoyl phenylethanoid glycoside from a medicinal herb Radix Rehmanniae, could promote IL-10 production from both human and murine B cells via critically regulating the TLR4/PI3K axis. Moreover, TLR4 was found increased in Breg cells from mice with experimental SS (ESS), a mouse model that recapitulates human pSS. Thus, B cells from the ESS mice were susceptible to AC treatment, showing higher IL-10-producing capacity than those from naïve controls. In addition, AC treatment also promoted the production of IL-10 from TLR4+ CXCR4+ plasma cells of ESS mice. Notably, we found that AC was able to enter lymphoid organs upon oral administration. AC treatment effectively increased IL-10+ B cells in ESS mice and ameliorated disease pathology accompanied by reduced T effector cells, including Th17 and T follicular helper cells in the ESS mice. In conclusion, AC could promote Breg cell function and attenuate ESS pathology in vivo, which may be a promising drug candidate for treating pSS and other autoimmune diseases.

MiR-325-3p mediate the CXCL17/CXCR8 axis to regulate angiogenesis in hepatocellular carcinoma.

INTRODUCTION: MicroRNA-325-3p (miR-325-3p) is involved in the progression of a great number of tumors. However, the regulatory mechanism of miR-325-3p on hepatocellular carcinoma (HCC) remains unclear. AIM: In this paper, we aim to investigate the underlying mechanism by which miR-325-3p regulate the progression of HCC. METHODS: RT-qPCR was performed to detect the levels of miR-325-3p, CXCL17, and CXCR8. Western bolt was conducted to determine the levels of pro-angiogenic factors VEGF, FGF2, Ang-1 and PDGF-B. Immunohistochemistry was carried to detect the distribution and expression of Ki-67 and CD34 in HCC tissues. MTT and colony formation were carried to evaluate cell proliferation, endothelial tube-formation assay was used detect tubule formation, and transwell assay was performed to evaluate cell migration and invasion ability. Dual-luciferase activity assay was used to verify the relationship between miR-325-3p and CXCL17. RESULTS: MiR-325-3p was down-regulated in HCC cells and tissues, miR-325-3p overexpression inhibited the proliferation, migration and invasion of HCC cells. Besides, miR-325-3p overexpression inhibited angiogenesis of HCC. CXCL17 is a direct target of miR-325-3p and partially mediates the effect of miR-325-3p on proliferation, migration, invasion and angiogenesis of HCC. CONCLUSION: MiR-325-3p regulated angiogenesis of HCC via mediating CXCL17/CXCR8 axis, indicating miR-325-3p may serve as a promising therapy biomarker for HCC.