NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells

Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis

Intraoral Perineurioma, Soft Tissue Type: Report of Five Cases, Including 3 Intraosseous Examples, and Review of the Literature

Soft tissue type perineuriomas (STP) are uncommon tumors, oral examples being very rare. They have been described in the mandible, gingiva, lips, retrotonsillar mucosa and maxillary vestibule. Herein, we report the clinicopathologic features of five STP, two affecting the buccal mucosa and three the mandible. Three patients were women and two men. All tumors were characterized by a proliferation of cytologically bland, mitotically inactive spindled cells with round, ovoid or spindled nuclei, embedded in a variably collagenous and myxoid matrix. Interestingly, two mandibular tumors featured psammoma bodies and one, in addition, contained irregular calcifications. Tumor cells showed the immunohistochemical profile of perineurial cells including epithelial membrane antigen, Glut-1, claudin-1 and collagen type IV. S100 and neurofilament proteins were not expressed by the tumor cells. A few minute, peripherally situated, entrapped nerves were identified. All tumors were reported gross-totally excised and no recurrences have taken place. The clinical characteristics of STP are summarized and its differential diagnosis relative to other spindle cells tumors and meningioma is discussed