Neuron-restricted cytomegalovirus latency in the central nervous system regulated by CD4+ T-cells and IFN-γKrstanović, Mihalić, Rashidi
et alJ Neuroinflammation (2025) 22 (1), 95
Abstract: All human herpesviruses establish latency following the resolution of the primary infection. Among these, α-herpesviruses HSV-1, HSV-2 and VZV establish latency in neurons, whereas neurons are not traditionally considered a site of latency for other herpesviruses. Using a combination of in vivo murine models and ex vivo human fetal tissues, we discovered that cytomegalovirus (CMV), a ubiquitous β-herpesvirus, can persist in neurons and that CD4+ T-cell-derived interferon-gamma is critical in restricting active viral replication in this cell type. Furthermore, we show that mouse CMV can establish latency in neurons and that CD4+ T-cells are essential in preventing viral reactivation. Our findings may have translational significance because human cytomegalovirus (HCMV) is the leading cause of congenital viral infections resulting in neurodevelopmental and neuroinflammatory lesions with long-term functional sequelae.© 2025. The Author(s).
Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretionMori, Ogino, Murakami
et alJ Gastroenterol (2025)
Abstract: Creeping fat is a characteristic of Crohn's disease and impacts the disease course. We evaluated creeping fat formation, focusing on innate lymphoid cell-mediated fibrogenesis and its clinical significance.Patients with inflammatory lesions in the ileum (the most commonly affected area), who underwent surgical resection at Osaka University or Hyogo Medical University (n = 34), were included. The ileum and mesentery were obtained from three sites: the control, non-creeping fat part, and creeping fat part. The distribution and properties of the innate lymphoid cells were analyzed by cell isolation. Furthermore, the correlation between macrophages and their effects on adipose tissue and clinical course were also investigated in a prospective cohort study.Group 1 innate lymphoid cells in creeping fat were increased, correlating with inflammatory macrophages in the mesentery and showing higher interferon-γ expression. Co-culture experiment involving stromal vascular fraction from the control mesentery and Group 1 innate lymphoid cells from creeping fat revealed increased mRNA expression of fibrosis-related genes and inflammatory markers of macrophages, although these changes were nullified by interferon-γ-neutralizing antibody. Next, we examined the clinical importance of Group 1 innate lymphoid cells and identified their high frequency in creeping fat as a risk factor for early recurrence (P = 0.008, odds ratio: 1.19). Furthermore, the higher Group 1 innate lymphoid cell frequency group (≥ 80%) had shorter relapse-free survival (P = 0.03).Group 1 innate lymphoid cells and inflammatory macrophages contribute to creeping fat formation via interferon-γ secretion, affecting post-surgery intestinal outcomes.© 2025. The Author(s).
Immunoinformatics method to design universal multi-epitope nanoparticle vaccine for TGEV S proteinLi, Yu, Xiao
et alSci Rep (2025) 15 (1), 10931
Abstract: Porcine transmissible enteritis virus (TGEV) is a fatal pathogen affecting newborn piglets, presenting a significant challenge to global intensive pig farming biosecurity due to its ongoing mutation. There is still a lack of effective vaccines to combat this virus, Vaccination has long been considered the most effective way to overcome infectious diseases, however, traditional vaccines cannot be brought to market quickly enough to deal with rapid mutations and emerging viruses. Therefore, this study addresses this gap by using immunoinformatics methods and ferritin nanoparticle delivery system to build a platform for rapid research and development of porcine coronavirus vaccine, designing a candidate nanoparticle vaccine that targets the TGEV S protein. To this end, multiple servers and strict screening criteria were used to analyze the S protein, and 3 CTL dominant epitopes, 3 Th dominant epitopes, and 6 B cell dominant epitopes were obtained. The candidate nanoparticle vaccine was constructed by incorporating ferritin sequences through the C-terminus after they were tandemly linked in a certain order using a flexible linker. Further experimental analyses showed that the designed candidate nanoparticle vaccine possessed relatively high antigenicity, immunogenicity, non-allergenicity, non-transmembrane proteins, suitable physicochemical properties, and high solubility upon overexpression. Tertiary structure modeling and disulfide engineering ensured conformational similarity to natural proteins and high stability. Additionally, the model predicted 6 Linear Epitopes and 6 Discontinuous Epitopes for B-cell conformational epitopes. Docking with TLR-3 and TLR-4 molecules shows a large number of interacting hydrogen-bonded amino acid residues and hydrophobically interacting amino acid residues. Immunomimetic assays show high levels of immunoglobulin, T-lymphocyte and IFN-γ secretion and may elicit specific immune responses. Through computerized cloning, the candidate nanoparticle vaccine can be efficiently expressed in the E. coli K12 expression system, aligning with future large-scale industrial production strategies. Overall, the results indicate that the constructed candidate nanoparticle vaccine can be effectively expressed and may be able to induce a strong immune response, which is expected to be an ideal candidate vaccine against TGEV.© 2025. The Author(s).
Blood single cell transcriptomic and proteomic signatures of paradoxical eczema in psoriasis patients treated with biologicsAl-Janabi, Martin, Simpson
et alJ Invest Dermatol (2025)
Abstract: Biologics targeting the tumour necrosis factor (TNF) and interleukin (IL)-17/23 axis are highly effective treatments for psoriasis but can result in cutaneous adverse events. The pathogenesis of paradoxical eczema, the occurrence of an atopic dermatitis phenotype after biologic initiation in people with psoriasis, is unknown. Using single cell RNA sequencing and mass cytometry, we found increased expression of TNF, interferon (IFN)-γ and IFN-α and their signalling pathways in paradoxical eczema case cell clusters compared with matched psoriasis controls. Genetic variants influencing expression of chemokine signalling and TNF pathway genes were associated with paradoxical eczema in a separate genotyped cohort, and this association was independent of known atopic risk loci. This suggests that paradoxical eczema has a predominantly type 1 systemic inflammatory signature, and that genetic susceptibility to aberrant chemokine and TNF pathway signalling could contribute to development of this phenotype during biologic treatment.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
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