Biology subjects

Pfeffer, P. E.

Publications and source records attributed to Pfeffer, P. E..

4 recordsLinked to original sources

bioRxiv2026

Characterisation of Peripheral Blood B Cell Receptor Repertoire in Severe Eosinophilic Asthma and EGPA

BackgroundSevere eosinophilic asthma (SEA), eosinophilic granulomatosis with polyangiitis (EGPA) and nasal polyposis (NP) are immune-mediated diseases characterised by eosinophilic inflammation. However, there is also increasing interest in the potential pathological roles of autoantibodies in these diseases. Understanding their B cell receptor (BCR) repertoires may provide valuable insights into disease mechanisms, and potential role of B cells in their pathology. MethodsWe conducted BCR repertoire sequencing using peripheral blood from 43 patients, comprising SEA with nasal polyps (SEA+NP), SEA without nasal polyps (SEA-NP), and EGPA, along with 16 healthy controls (HCs). ResultsCompared to HCs, patients with EGPA exhibited increased relative proportions of IgA1, IgG1, IgG2, and IgG4 subclasses. Similarly, SEA-NP patients demonstrated significantly high proportion of IgG2 sequences. Notably, the IgG4 subclass was significantly elevated across all patient groups compared to HCs. Patients receiving anti-IL-5/5R biologic treatments showed increased relative proportions of IgA2 and IgG2 subclasses compared to untreated patients. Some variation across participant groups in mean somatic hypermutation and mutation frequency was evident. 1,508 clones shared across patients, but not healthy controls, were evident though the majority showed low clonal expansion. Nevertheless, a few shared clones did show either high prevalence across patients and/or higher clonal expansion. ConclusionChanges in BCR repertoires in SEA/EGPA are consistent with a pattern of a more mature B cell component in the periphery and with the T2 inflammatory response observed in SEA and EGPA. BCR clonotypes shared across patients were evident, however, whether such clonotypes are pathological in SEA/EGPA requires further investigation.

immunology↗

bioRxiv2025

Age-associated inflammatory monocytes are increased in menopausal females and reversed by Hormone Replacement Therapy

Biological sex is a crucial, but poorly understood variable in age-related susceptibility to infections and chronic inflammation - inflammageing. Monocytes are important immune cells responsible for initiating and resolving inflammatory responses to infection. While changes in monocyte populations result in increased susceptibility to infection, there is limited research on the impact of age and sex on human monocyte phenotype and function. The aim of this work was to dissect the impact of increasing age and biological sex on human monocyte phenotype and function. Here we show that older females have increased inflammatory intermediate and non-classical monocytes compared to young. These monocyte subsets were the most inflammatory ex vivo and their frequency correlated with markers of systemic inflammation. Proteomic analysis of sorted monocyte populations demonstrated that the three human monocyte subsets have largely distinct phenotypes. Additionally, proteomic analysis identified key age-associated protein pathways, including complement cascade and phagocytosis, downregulated in monocytes from older compared to younger individuals. We confirmed the proteomics findings showing that circulating C3 concentrations were reduced with age in females but not males. This decrease in complement in older females resulted in reduced monocyte phagocytosis. Crucially, we demonstrate that in peri/menopausal females, Hormone Replacement Therapy (HRT) reversed this expansion in intermediate monocytes and decreased circulating CRP as compared to age matched controls. Importantly peri/menopausal females on HRT had increased C3 serum concentrations and significantly improved monocyte phagocytosis. The data presented here indicate the importance of menopause in ageing monocyte phenotype and function. This data highlights the potential use of HRT in restoring monocyte function in females during ageing.

immunology↗

bioRxiv2020

Physiological and transcriptomic response of Medicago truncatula to high and low benefit mycorrhizal fungi

Arbuscular mycorrhizal (AM) fungi form a root endosymbiosis with many agronomically important crop species and both enhance the ability of their host to obtain nutrients from the soil and increase host tolerance to biotic and abiotic stressors. However, AM fungal species differ in the benefits they provide to their host plants. Here, we examined the putative molecular mechanisms involved in the regulation of the physiological response of Medicago truncatula to either Rhizophagus irregularis or Glomus aggregatum, a high or a low benefit AM fungus, respectively. Colonization with R. irregularis led to higher growth and nutrient uptake benefits than the colonization with G. aggregatum. These benefits were linked to an elevated expression in the roots of genes involved in strigolactone biosynthesis (NSP1, NSP2, CCD7, and MAX1a), mycorrhiza-induced phosphate (PT8), ammonium (AMT2;3), and nitrate (NPF4.12) transporters and the putative ammonium transporter NIP1;5. R. irregularis also stimulated the expression of photosynthesis-related genes in the shoot and the upregulation of the sugar transporters SWEET1.2, SWEET3.3 and SWEET 12 and the lipid biosynthesis gene RAM2 in the roots. In contrast, G. aggregatum induced the expression of biotic stress defense response genes in the shoots and several genes associated with abiotic stress in the roots. This suggests that either the host perceives colonization by G. aggregatum as a pathogen attack or that G. aggregatum can prime host defense responses. Our findings reveal novel insights into the molecular mechanisms that control the host plant response to colonization with high- and low-benefit arbuscular mycorrhizal fungal symbionts.

plant biology↗

bioRxiv2018

Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter.

BackgroundParticulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.\n\nObjectivesMechanistic cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways.\n\nMethodsTranscriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D.\n\nResultsTranscriptome analysis identified over 500 genes significantly perturbed by PM-stimulation, including multiple pro-inflammatory cytokines. Vitamin D altered expression of a subset of these PM-induced genes, including suppressing IL6. Addition of vitamin D suppressed PM-stimulated IL-6 production, although to significantly greater extent in healthy versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, supporting a role for this pathway in the anti-inflammatory actions of vitamin D.\n\nConclusionsIn a study using HBECs from 18 donors, vitamin D enhanced HBEC antioxidant responses and modulated the immune response to PM, suggesting that vitamin D may protect the airways from pathological pollution-induced inflammation.

immunology↗