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Schizophyllum commune is a widely distributed basidiomycete fungus that occasionally causes sinusitis or allergic bronchopulmonary mycosis. The invasive infection mostly occurs in immunocompromised adults. The number of reports on S. commune infection have increased in this decade due to the expansion of diagnostic techniques and awareness in clinical practice. However, S.commune infection in patients with primary immunodeficiencies has not been reported yet. Here, we described S. commune -abscesses developed in the brain and lung of a boy with chronic granulomatous disease (CGD) after allogenic hematopoietic cell transplantation (HCT). A 12-year-old CGD patient developed febrile neutropenia from day 4 after HCT, followed by chest pain on day 23. He had no obvious infection before HCT. Diagnostic imaging revealed disseminated lung and brain abscesses. He received administration of voriconazole, and his symptoms improved after engraftment. Chronic administration of voriconazole had also a favorable therapeutic response to brain lesion. A part of the fungus ball exhaled by the patient was cultured to develop a filamentous fungus. S. commune was identified by the analysis of the 28S rRNA gene. The catalase test was positive for S. commune , indicating that S. commune had virulence in this patient with CGD. The assessment of specific-IgG to S. commune suggested peri-transplant infection, although colonization was not excluded. This rare pediatric case of S. commune infection highlights that CGD patients are vulnerable to invasive infection, especially when undergoing HCT. [ABSTRACT FROM AUTHOR]

Treating ocular involvement in eosinophilic granulomatosis with polyangiitis (EGPA) can be challenging. We present the case of a 37-year-old woman with EGPA who had severe bilateral visual field defects. Laboratory results showed leukocytosis (17,500 WBC/μL, 25.8 % eosinophils), negative MPO-ANCA titer, and elevated PR3-ANCA level (33.2 IU/mL). Diffusion-weighted MRI revealed bilateral hyperintense occipital lesions, which were more prominent on the left. Her therapy initially included a steroid pulse, followed by daily prednisolone, but her visual field defects remained refractory. The addition of intravenous cyclophosphamide (5 courses) and intravenous immunoglobulin decreased her optic neuropathy and resolved her visual field defects. [ABSTRACT FROM AUTHOR]

• Non-neuronal nAChRs are involved in ISC proliferation and differentiation. • Deletion of the nicotinic β4 subunit (Chrnb4) leads to inhibition of organoid growth and differentiation. • nAChR signaling controls Hippo and Notch signaling pathways in Paneth cells. • Intestinal homeostasis and regulation are maintained by a three-part mechanism. Recent studies have shown that various mammalian non-neuronal cells synthesize acetylcholine (ACh) in situ and operate cholinergic signaling via nicotinic and muscarinic ACh receptors (nAChRs and mAChRs). Understanding the mechanisms that control intestinal stem cell (ISC) function through activation of nAChR signaling is critical for developing therapeutic interventions for diseases such as inflammatory bowel disease (IBD). Previously, by conducting RNA sequencing (RNA-Seq) analysis using crypt-villus organoid cultures, we found that the Hippo signaling pathway, a stem cell regulating network, is upregulated in ISCs after treatment with nicotine. Here, we explored the roles of nAChR signaling through activation of the Hippo signaling pathway. RNA-Seq data were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. β4-knock-in mice were generated, and experiments using the knock-in mice and their intestinal organoids were carried out. RNA-Seq and qRT-PCR analyses demonstrated that the expression of YAP1/TAZ and Notch1/Dll1 was upregulated after treatment with nicotine. However, a nAChR antagonist, mecamylamine, strongly inhibited the expression of these genes. Notably, we found that in β4-knock-in mouse small intestines, expression of YAP1 and Notch1 was significantly reduced, but not that of TAZ and Dll1 , suggesting that Hippo and Notch signaling pathways are putative targets for nAChR signaling. Furthermore, fluorescent signals were detected in Paneth cells that interact with ISCs at the crypt bottom, indicating an interaction between Paneth cells and ISCs via nAChR signaling through the activation of Hippo and Notch signaling pathways. Our results indicate that upregulated nAChR signaling contributes to the maintenance of ISC activity and balances differentiation through activation of Hippo and Notch signaling pathways. [ABSTRACT FROM AUTHOR]

Intestinal microfold cells (M cells) in Peyer's patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand (RANKL) expressed on mesenchymal cells triggers differentiation into M cells, other environmental cues remain unknown. Here, we show that the metastasis-promoting protein S100A4 is required for development of mature M cells. S100A4-producing cells are a heterogenous cell population including lysozyme-expressing dendritic cells and group 3 innate lymphoid cells. We found that in the absence of DOCK8, a Cdc42 activator critical for interstitial leukocyte migration, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells. While S100A4 promotes differentiation into mature M cells in organoid culture, genetic inactivation of S100a4 prevents the development of mature M cells in mice. Thus, S100A4 is a key environmental cue that regulates M cell differentiation in collaboration with RANKL. • DOCK8 plays a key role in the development of mature M cells in Peyer's patches • DOCK8 controls the localization of S100A4-producing cells in the subepithelial dome • S100A4 protein promotes M cell maturation in organoid culture • Deficiency of S100A4 prevents the development of mature M cells in mice Kunimura et al. find that in the absence of DOCK8, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells in Peyer's patches. In vitro and in vivo studies demonstrate that S100A4 protein is a key environmental factor that promotes M cell maturation. [ABSTRACT FROM AUTHOR]

Green leaf volatiles (GLVs) are C6-aliphatic aldehydes/alcohols/acetates, and biosynthesized from the central precursor fatty acid 13-hydroperoxides by 13-hydroperoxide lyases (HPLs) in various plant species. While GLVs have been implicated as defense compounds in plants, GLVs give characteristic grassy note to a bouquet of aroma in green tea, which is manufactured from young leaves of Camellia sinensis . Here we identify three HPL- related genes from C. sinensis via RNA-Sequencing (RNA-Seq) in silico , and functionally characterized a candidate gene, CYP74B24 , as a gene encoding tea HPL. Recombinant CYP74B24 protein heterologously expressed in Escherichia coli specifically produced ( Z )-3-hexenal from 13-HPOT with the optimal pH 6.0 in vitro . CYP74B24 gene was expressed throughout the aerial organs in a rather constitutive manner and further induced by mechanical wounding. Constitutive expression of CYP74B24 gene in intact tea leaves might account for low but substantial and constitutive formation of a subset of GLVs, some of which are stored as glycosides. Our results not only provide novel insights into the biological roles that GLVs play in tea plants, but also serve as basis for the improvement of aroma quality in tea manufacturing processes. [ABSTRACT FROM AUTHOR]