Explore the vast range of titles available.

Glial cells of the enteric nervous system (ENS) interact closely with the intestinal epithelium and secrete signals that influence epithelial cell proliferation and barrier formation in vitro. Whether these interactions are important in vivo, however, is unclear because previous studies reached conflicting conclusions (Prochera and Rao, 2023). To better define the roles of enteric glia in steady state regulation of the intestinal epithelium, we characterized the glia in closest proximity to epithelial cells and found that the majority express the gene Proteolipid protein 1 ( PLP1 ) in both mice and humans. To test their functions using an unbiased approach, we genetically depleted PLP1 + cells in mice and transcriptionally profiled the small and large intestines. Surprisingly, glial loss had minimal effects on transcriptional programs and the few identified changes varied along the gastrointestinal tract. In the ileum, where enteric glia had been considered most essential for epithelial integrity, glial depletion did not drastically alter epithelial gene expression but caused a modest enrichment in signatures of Paneth cells, a secretory cell type important for innate immunity. In the absence of PLP1 + glia, Paneth cell number was intact, but a subset appeared abnormal with irregular and heterogenous cytoplasmic granules, suggesting a secretory deficit. Consistent with this possibility, ileal explants from glial-depleted mice secreted less functional lysozyme than controls with corresponding effects on fecal microbial composition. Collectively, these data suggest that enteric glia do not exert broad effects on the intestinal epithelium but have an essential role in regulating Paneth cell function and gut microbial ecology.

Kaposiform hemangioendothelioma is a distinctive vascular neoplasm affecting predominantly children and neonates. In neonates it needs to be differentiated from common infantile hemangioma and other vascular lesions of infancy. Kaposiform hemangioendothelioma immunoreacts with vascular endothelial growth factor receptor 3, and partial lymphothelial differentiation of this lesion has been suggested. D2-40 has been recently proposed as a selective marker of lymphatic endothelium. We performed immunohistochemical analysis with the D2-40 antibody on 24 kaposiform hemangioendotheliomas and 48 other pediatric vascular lesions including common infantile hemangioma (n=10), rapidly involuting congenital hemangioma (n=10), noninvoluting congenital hemangioma (n=9), verrucous hemangioma (n=9), and pyogenic granuloma (n=10) to define whether this marker can be applied in the diagnosis of vascular lesions of infancy. In all, 23 of 24 (96%) kaposiform hemangioendotheliomas exhibited a distinct staining, while none of the other lesions immunoreacted with D2-40. D2-40 stained the neoplastic spindled cells and lymphatic channels adjacent to vascular lobules of kaposiform hemangioendothelioma. These findings support D2-40 as a new determinate marker for kaposiform hemangioendothelioma, useful in differentiating it from other vascular lesions of infancy and suggest lymphothelial differentiation of the neoplastic component of kaposiform hemangioendothelioma. Further studies are necessary to define the identity of the D2-40 antigen and to elucidate the biologic significance of its selective lymphothelial reactivity.

Glial cells of the enteric nervous system (ENS) interact closely with the intestinal epithelium and secrete signals that influence epithelial cell proliferation and barrier formation in vitro. Whether these interactions are important in vivo, however, is unclear because previous studies reached conflicting conclusions (Prochera and Rao, 2023). To better define the roles of enteric glia in steady state regulation of the intestinal epithelium, we characterized the glia in closest proximity to epithelial cells and found that the majority express the gene Proteolipid protein 1 ( PLP1 ) in both mice and humans. To test their functions using an unbiased approach, we genetically depleted PLP1 + cells in mice and transcriptionally profiled the small and large intestines. Surprisingly, glial loss had minimal effects on transcriptional programs and the few identified changes varied along the gastrointestinal tract. In the ileum, where enteric glia had been considered most essential for epithelial integrity, glial depletion did not drastically alter epithelial gene expression but caused a modest enrichment in signatures of Paneth cells, a secretory cell type important for innate immunity. In the absence of PLP1 + glia, Paneth cell number was intact, but a subset appeared abnormal with irregular and heterogenous cytoplasmic granules, suggesting a secretory deficit. Consistent with this possibility, ileal explants from glial-depleted mice secreted less functional lysozyme than controls with corresponding effects on fecal microbial composition. Collectively, these data suggest that enteric glia do not exert broad effects on the intestinal epithelium but have an essential role in regulating Paneth cell function and gut microbial ecology.

Glial cells of the enteric nervous system (ENS) interact closely with the intestinal epithelium and secrete signals that influence epithelial cell proliferation and barrier formation . Whether these interactions are important however, is unclear because previous studies reached conflicting conclusions [1]. To better define the roles of enteric glia in steady state regulation of the intestinal epithelium, we characterized the glia in closest proximity to epithelial cells and found that the majority express in both mice and humans. To test their functions using an unbiased approach, we genetically depleted PLP1 cells in mice and transcriptionally profiled the small and large intestines. Surprisingly, glial loss had minimal effects on transcriptional programs and the few identified changes varied along the gastrointestinal tract. In the ileum, where enteric glia had been considered most essential for epithelial integrity, glial depletion did not drastically alter epithelial gene expression but caused a modest enrichment in signatures of Paneth cells, a secretory cell type important for innate immunity. In the absence of PLP1 glia, Paneth cell number was intact, but a subset appeared abnormal with irregular and heterogenous cytoplasmic granules, suggesting a secretory deficit. Consistent with this possibility, ileal explants from glial-depleted mice secreted less functional lysozyme than controls with corresponding effects on fecal microbial composition. Collectively, these data suggest that enteric glia do not exert broad effects on the intestinal epithelium but have an essential role in regulating Paneth cell function and gut microbial ecology.

Kaposiform hemangioendothelioma is a distinctive vascular neoplasm affecting predominantly children and neonates. In neonates it needs to be differentiated from common infantile hemangioma and other vascular lesions of infancy. Kaposiform hemangioendothelioma immunoreacts with vascular endothelial growth factor receptor 3, and partial lymphothelial differentiation of this lesion has been suggested. D2-40 has been recently proposed as a selective marker of lymphatic endothelium. We performed immunohistochemical analysis with the D2-40 antibody on 24 kaposiform hemangioendotheliomas and 48 other pediatric vascular lesions including common infantile hemangioma (n=10), rapidly involuting congenital hemangioma (n=10), non-involuting congenital hemangioma (n=9), verrucous hemangioma (n=9), and pyogenic granuloma (n=10) to define whether this marker can be applied in the diagnosis of vascular lesions of infancy. In all, 23 of 24 (96%) kaposiform hemangioendotheliomas exhibited a distinct staining, while none of the other lesions immunoreacted with D2-40. D2-40 stained the neoplastic spindled cells and lymphatic channels adjacent to vascular lobules of kaposiform hemangioendothelioma. These findings support D2-40 as a new determinate marker for kaposiform hemangioendothelioma, useful in differentiating it from other vascular lesions of infancy and suggest lymphothelial differentiation of the neoplastic component of kaposiform hemangioendothelioma. Further studies are necessary to define the identity of the D2-40 antigen and to elucidate the biologic significance of its selective lymphothelial reactivity..