Biology subjects

Rosser, E. C.

Publications and source records attributed to Rosser, E. C..

4 recordsLinked to original sources

bioRxiv2025

Spatially resolved fetal and maternal cell contributions to severe Preeclampsia

The molecular and cellular pathophysiology of the fetal-maternal interface in preeclamsia remains poorly understood, but it is increasingly clear that both fetus and mother make independent contributions to it. Here, we spatially distinguish them from each other and from gestational age for the severe form of the disease, interrogating tissues and cell types beyond the placenta for the Early and Late presentation of the condition. In addition to concerted hypoxia, angiogenic imbalance, fibrosis and aberrant metabolism in the placenta, new maternal immune signatures, including changes in macrophages, mitochondrial dysfunction and interferon signalling in the placenta, myometrium or chorioamniotic membranes, offer an explanation to systemic inflammation and endothelial dysfunction in the mother. These tissue and cell-specific responses are potential targets for therapy, with their prompt consideration in Early gestational disease likely beneficial due to its severity. Thus, timely intervention during gestation could change the extremely poor prognosis of severe disease.

molecular biology↗

bioRxiv2024

Oestrogen influences B cell class-switching in individuals with an XX sex chromosome complement

Sex differences in humoral immunity are well-documented, though the mechanisms underpinning these differences remain ill-defined. Here, we demonstrate that post-pubertal cisgender females have higher levels of class-switched B cells compared to age-matched cisgender males. However, whilst sex chromosome-encoded genes characterise most of the differences in total B cell transcriptomes between cisgender-females and -males, sex differences in class-switched B cells are only observed post-pubertally. Accordingly, B cells express high levels of oestrogen receptor 2 (ESR2) and genes known to regulate B cell class-switching are enriched for ESR2-binding sites. Using a gender-diverse cohort of young people, we show that in transgender males (XX chromosomal background), blockade of natal oestrogen reduced the frequency of class-switched B cells, whilst gender-affirming oestradiol treatment in transgender females (XY chromosomal background), did not increase the frequency of class-switched B cells. These data demonstrate that sex hormones and chromosomes work in tandem to impact immune responses, with oestrogen only supporting B cell class-switching on an XX chromosomal background. eTOC summarySex hormones and chromosomes work in tandem to impact immune responses, with oestrogen influencing B cell class-switching exclusively on an XX chromosomal background.

immunology↗

bioRxiv2024

Treg fitness as a biomarker for disease activity in Juvenile Idiopathic Arthritis

Juvenile Idiopathic Arthritis (JIA) is an autoimmune condition characterised by persistent flares of joint inflammation. However, no reliable biomarker exists to predict the erratic disease course. Normally, regulatory T cells (Tregs) maintain immune tolerance, with altered Tregs associated with autoimmunity. Treg signatures have shown promise in monitoring other autoimmune conditions, therefore a Treg gene and/or protein signature could offer novel biomarker potential for predicting disease activity in JIA. Machine learning on our nanoString Treg gene signature on peripheral blood (PB) Tregs generated a model to distinguish active JIA (active joint count, AJC[≥]1) Tregs from healthy controls (HC, AUC=0.9875). Biomarker scores from this model successfully differentiated inactive (AJC=0) from active JIA PB Tregs. Moreover, scores correlated with clinical activity scores (cJADAS), and discriminated subclinical disease (AJC=0, cJADAS[≥]0.5) from remission (AUC=0.8980, Sens=0.8571, Spec= 0.8571). To investigate altered Treg fitness in JIA by protein expression, we utilised spectral flow cytometry and unbiased analysis. Three Treg clusters were increased in active JIA PB, including CD226highCD25low effector-like Tregs and CD39-TNFR2-Helioshigh, while a 4-1BBlowTIGITlowID2intermediate Treg cluster predominated in inactive JIA PB (AJC=0). The ratio of these Treg clusters correlated to cJADAS, and higher ratios could predict inactive individuals that flared by 6-month follow-up. Thus, we demonstrate altered Treg signatures and subsets as an important factor, and useful biomarker, for disease progression versus remission in JIA, revealing genes and proteins important in Treg fitness. Ultimately, PB Treg fitness measures could serve as routine biomarkers to guide disease and treatment management to sustain remission in JIA.

immunology↗

bioRxiv2018

A novel innate lymphoid cell delineates childhood autoimmune arthritis

Inflammation in autoimmune disease is mediated by a complex network of interacting cells. Their identity and cross-talk are encoded in messenger RNA (mRNA). Juvenile idiopathic arthritis (JIA), a chronic autoimmune arthritis of childhood, is characterised by synovial inflammation with infiltration of both innate and adaptive immune cells1. Activated T cells play a role in disease2 but the cell types that drive the recruitment and activation of immune cells within the synovium are not known. Here, we utilised droplet-based and full length single cell mRNA sequencing to obtain a quantitative map of the cellular landscape of JIA. We studied 45,715 cells from the synovial fluid of inflamed knee joints and peripheral blood. We identified a population of synovial innate lymphoid cells (ILCs), shared across patients, that exhibited a unique transcriptional profile in comparison to canonical ILC subtypes. Validation at protein-level across a spectrum of autoimmune arthritides revealed that these ILCs are pathologically expanded in a particular type of JIA. Using statistical tools to assess cellular interactions in synovial fluid, ILCs emerged as a central node of communication, expressing the full repertoire of genes required to orchestrate and maintain the inflammatory milieu. Several ILC-mediated signalling pathways may lend themselves as novel therapeutic targets. Together our findings demonstrate a distinct ILC subtype associated with a tissue-specific childhood autoimmune disease.

immunology↗