Biology subjects

Cairns, E.

Publications and source records attributed to Cairns, E..

4 recordsLinked to original sources

bioRxiv2026

Fungicide and warming interact to reduce soil ecosystem functioning

Soil microbial communities are essential to the functioning of their ecosystems, providing vital services such as plant growth promotion and bioremediation. However, intensively managed environments such as agricultural soils are increasingly challenged with multiple harsh environmental stressors from the compounding effects of climate change and conventional agricultural practices. Understanding how soil communities will respond to environmental stress along multiple axes is key for predicting how environmental change will impact terrestrial soil ecosystems. We combine experimental evolution with community phenotyping, 16s rRNA metabarcoding, fungicide resistance assays and plant experiments, to show that fungicide and warming temperatures together drive a synergistic reduction in soil community respiration rates, metabolic capacity and plant growth promotion (Hordeum vulgare), which would have been missed by looking at stressor effects independently. Dual stressors caused widespread loss of metabolic activity, particularly for carbohydrates and carboxylic acids, highlighting impairment of community function. Fungicide-evolved soil isolates had a 16-fold increase in fungicide resistance, but only in the absence of warming - suggesting that the dual stressor treatment constrained fungicide adaptation. Together, our findings suggest that the number of stressors (rather than the nuances of individual stressors) may be key for predicting soil microbial community responses to environmental change across multiple axes.

ecology↗

bioRxiv2025

Homocitrullinated Peptides Drive Pro-Inflammatory T-Cell Responses in a Humanized Mouse Model of Rheumatoid Arthritis

ObjectiveAnti-homocitrullinated protein/peptide antibodies (AHCPA) are specific to rheumatoid arthritis (RA) and predictive of worse prognosis, suggesting a pathogenic role for autoreactivity to homocitrullinated antigens. However, T-cell responses to homocitrullinated peptides remain largely unexplored. We investigated these responses in a humanized HLA-DR4-transgenic (DR4tg) mouse model of RA, which expresses the strongest genetic risk factor for this disease. MethodsDR4tg mice were injected subcutaneously with a homocitrullinated peptide called HomoCitJED while control mice received phosphate-buffered saline. After 10 days, T-cells were analyzed for their phenotypic characteristics, cytokine production, and proliferative capacities in the draining lymph nodes (dLNs) and spleens by flow cytometry, enzyme-linked immunosorbent assays, and ProQuantum immunoassays. ResultsHomoCitJED immunization drove robust expansion of T helper (Th) 1, Th17 and hybrid Th1/Th17 CD4+ T cells in dLNs, alongside elevated CD25 activation marker within these subsets. Intracellular cytokine staining confirmed effector activity, revealing higher frequencies of IL-17A+, TNF-+IL-17A+, and IFN-{gamma}+IL-17A+ CD4+ T cells. CD4+ T cells from dLNs also up-regulated the exhaustion markers LAG-3 and Tim-3. CD8+ T cells (Tc) mirrored these findings, as HomoCitJED immunization augmented CD25 and KLRG1 expression, Tc1/Tc17-type IL-17A and IFN-{gamma}/IL-17A production, and antigen-specific proliferation. Additionally, Tim-3, LAG-3 and PD-1 expression on these subsets was augmented. ConclusionsA homocitrullinated peptide elicited Th1/Th17 and Tc1/Tc17 responses marked by concurrent activation and exhaustion signatures, pointing to a dysregulated T-cell state. These findings position homocitrulline-driven T-cell imbalance across both CD4+ and CD8+ T-cell compartments as a potential mechanistic contributor to RA pathogenesis and a target for future immunomodulatory therapies.

immunology↗

bioRxiv2025

Immune Responses Targeting Homocitrullinated Peptides Drive Rheumatoid Arthritis-like Pathology in HLA-DR4 Transgenic Mice

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. A hallmark feature of RA is the presence of anti-citrullinated protein autoantibodies (ACPAs), which have been extensively studied in disease pathogenesis. The development of these autoantibodies is strongly associated with the expression of HLA-DR4, containing the shared epitope. More recently, anti-homocitrullinated protein autoantibodies (AHCPAs) have also been implicated in RA and demonstrate a similar genetic association. Therefore, this study aimed to evaluate the role of homocitrulline immune responses in RA pathogenesis. HLA-DR4 transgenic (DR4tg) and B6 mice were immunized with a synthetic homocitrullinated peptide (HomoCitJED) or PBS followed by a booster 21 days later. Beginning on day 75 post-primary immunization mice received knee intra-articular (i.a.) injections of HomoCitJED once a week for three consecutive weeks. Swelling post i.a. injection was measured using digital calipers. IgG antibodies against homocitrullinated peptides/proteins were measured using enzyme-linked immunosorbent assay (ELISA). Knees were sectioned and analyzed for histopathological damage and citrullinated/homocitrullinated protein levels. HomoCitJED immunized DR4tg mice exhibited significantly greater swelling and incidence of anti-HomoCitJED and -homocitrullinated fibrinogen IgG autoantibodies. Additionally, 30% had responses against CitJED, a synthetic citrullinated peptide. HomoCitJED immunized DR4tg mice also experienced greater total histopathological damage; however, the immunizations/injections did not affect citrullinated/homocitrullinated protein levels. In conclusion, homocitrulline-specific immune responses can induce RA-like disease in DR4tg mice, supporting the pathogenic role of AHCPAs in RA.

immunology↗

bioRxiv2021

IgA Potentiates NETosis in Response to Viral Infection

IgA is the second most abundant antibody present in circulation and is enriched at mucosal surfaces. As such, IgA plays a key role in protection against a variety of mucosal pathogens, including viruses. In addition to neutralizing viruses directly, IgA can also stimulate Fc-dependent effector functions via engagement of Fc alpha receptors (FcRI) expressed on the surface of certain immune effector cells. Neutrophils are the most abundant leukocyte, express FcRI, and are often the first to respond to sites of injury and infection. Here, we describe a novel function for IgA:virus immune complexes (ICs) during viral infections. We show that IgA:virus ICs potentiate NETosis - the programmed cell death pathway through which neutrophils release neutrophil extracellular traps (NETs). Mechanistically, IgA:virus ICs potentiated a suicidal NETosis pathway via engagement of FcRI on neutrophils through a toll-like receptor (TLR)-independent, NADPH oxidase complex-dependent pathway. NETs also were capable of trapping and inactivating viruses, consistent with an antiviral function.

immunology↗