Search

Sensitization and challenge using dinitrofluorobenzene (DNFB) induce contact hypersensitivity (CHS) with Th1 cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. In this study, we attempted to determine the role of CXCR3, a chemokine receptor, in Th1- and Th2-type CHS induced by DNFB or FITC using CXCR3-deficient (CXCR3-/-) mice. Ear swelling was prolonged after DNFB challenge in CXCR3-/- mice, which was accompanied by increased Th1 cytokines and decreased TGF-β and IL-10 expression at a late time point of CHS, whereas there was no significant difference between wild-type and CXCR3-/- mice in FITC-induced CHS. In Th1-type CHS, the number of regulatory T cells (Tregs) was decreased in the challenged ear of CXCR3-/- mice compared with that of wild-type mice, suggesting that CXCR3 would be important in migration of Tregs into the site of inflammation. Moreover, we examined the characteristics of CXCR3+ Tregs both in vitro and in vivo, revealing that CXCR3+ Tregs expressed high levels of TGF-β and IL-10 as well as IFN-? compared with CXCR3- Tregs. When CXCR3-/- mice were injected with CXCR3+ Tregs, the prolonged ear swelling induced by DNFB was normalized. Taken together, our results suggest that CXCR3+ Tregs play a key role for quenching Th1-type CHS. [ABSTRACT FROM AUTHOR]

Transcription factors (TFs) are able to regulate differentiationrelated processes, including dedifferentiation and direct conversion, through the regulation of cell type-specific transcriptional profiles. However, the functional interactions between the TFs regulating different transcriptional profiles are not well understood. Here, we show that the TFs capable of inducing cell type-specific transcriptional profiles prevent the dedifferentiation induced by TFs for pluripotency. Of the large number of TFs expressed in a neurallineage cell line, we identified a subset of TFs that, when overexpressed, strongly interfered with the dedifferentiation triggered by the procedure to generate induced pluripotent stem cells. This interference occurred through a maintenance mechanism of the cell type-specific transcriptional profile. Strikingly, the maintenance activity of the interfering TF set was strong enough to induce the cell line-specific transcriptional profile when overexpressed in a heterologous cell type. In addition, the TFs that interfered with dedifferentiation in hepatic-lineage cells involved TFs with known induction activity for hepatic-lineage cells. Our results suggest that dedifferentiation suppresses a cell type-specific transcriptional profile, which is primarily maintained by a small subset of TFs capable of inducing direct conversion. We anticipate that this functional correlation might be applicable in various cell types and might facilitate the identification of TFs with induction activity in efforts to understand differentiation. [ABSTRACT FROM AUTHOR]

We have succeeded in culturing dermal papilla (DP) cells long term and developed new techniques that enhance their hair follicle-inducing efficiency in a patch assay. The outgrowing DP cells from mouse vibrissae were markedly stimulated by 10 fetal bovine serum–Dulbecco's modified essential medium that included fibroblast growth factor-2 (FGF-2). Moreover, the potency of proliferation was maintained during serial cultivations (more than 30 passages). We combined these established DP cells with epidermal cells and implanted them subcutaneously into athymic mice to examine their hair follicle–inducing ability. New hair follicles were induced by dissociated DP cells at earlier passages (under passage 4), but the cells from later passages could not induce follicles. We next aggregated the DP cells to form spheres and then injected them with epidermal cells. Unlike the dissociated DP cells, the spheres made from the later passaged cells (more than 10 passages) did induce new hair follicles. We examined several genes specific for DP of anagen follicles and confirmed that their expression level was elevated in the spheres compared with their expression level in adherent DP cells. These results suggest that FGF-2 is essential for dermal papilla cell culture and that sphere formation partially models the intact DP, resulting in hair follicle induction, even by later passaged cells. [ABSTRACT FROM AUTHOR]

CD83 is a member of the Ig superfamily expressed primarily by mature dendritic cells (DCs). In mice, CD83 expression by thymic stromal cells regulates CD4 T cell development, with CD83−/− mice demonstrating dramatic reductions in both thymus and peripheral CD4 T cells. In this study, CD83 expression was also found to affect MHC class II antigen expression within the thymus and periphery. CD83 deficiency reduced cell-surface class II antigen expression by 25–50% on splenic B cells and DCs, thymic epithelial cells and peritoneal macrophages. Reduced class II expression was a stable and intrinsic property that resulted from increased internalization of class II from the surface of CD83−/− B cells. Otherwise, class II antigen transcription, intracellular expression, heterodimer structure, antigen processing and antigen presentation were normal. Reduced class II antigen expression was not the primary cause of the CD83−/− phenotype since thymocyte and peripheral T cell development was normal in class II− mice. Comparable blocks in CD4 thymocyte development were also observed in CD83−/− and CD83−/−class II− littermates. TCR and CD69 expression patterns in CD83−/− mice further suggested that double-positive thymocytes proceed through the class II-dependent stages of positive selection in the absence of CD83. These studies further emphasize a role for CD83 in lymphocyte development and immune regulation and reveal an unexpected role for CD83 expression in influencing cell-surface MHC class II turnover. [ABSTRACT FROM AUTHOR]