BackgroundInterleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.MethodsEAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA.ResultsHere we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA.ConclusionIL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions.
Although a benign syringofibroadenoma has been recognized as an eccrine tumor exhibiting net-like ductal proliferation embedded in fibroma-like stroma, a malignant counterpart has not been described heretofore. An 82-year-old man with severely sun-damaged skin had a 3 cm plaque in the dorsum of his left hand. The clinical diagnosis was squamous cell carcinoma. Histologically, the lesion was a bowenoid squamous cell carcinoma, both in situ (Bowen's disease-like) and bluntly invasive, with a concurrent phase showing unequivocal and widespread ductal differentiation, local expression of carcinoembryonic antigen, and sclerotic stroma. This syringofibrocarcinoma also impinged laterally on a mature and benign syringofibroadenoma and occurred above a minute deep dermal trichoepithelioma. This report presents a probably unrecognized new malignant tumor, clearly distinct yet related to both squamous cell carcinoma and eccrine carcinoma. Because its organoid architecture and the resemblance to and impingement on syringofibroadenoma, the term syringofibrocarcinoma is proposed.
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