Biology subjects

Moreland, L.

Publications and source records attributed to Moreland, L..

3 recordsLinked to original sources

bioRxiv2023

Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in At-Risk populations prior to clinical disease onset is crucial to establishing effective prevention strategies. Here, we applied mass cytometry to deeply characterize the immunophenotypes in blood from At-Risk individuals identified through the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared to established RA (n=67), and healthy controls (n=48). We identified significant cell expansions in At-Risk individuals compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5low naive B cell population was expanded in ACPA-positive FDRs. Further, we developed an "RA immunophenotype score" classification method based on the degree of enrichment of cell states relevant to established RA patients. This score significantly distinguished At-Risk individuals from controls. In all, we systematically identified activated lymphocyte phenotypes in At-Risk individuals, along with immunophenotypic differences among both ACPA+ and ACPA-FDR At-Risk subpopulations. Our classification model provides a promising approach for understanding RA pathogenesis with the goal to further improve prevention strategies and identify novel therapeutic targets.

genomics↗

bioRxiv2020

Robust design capture-recapture analysis of abundance and demographic parameters of Indian River Lagoon common bottlenose dolphins (Tursiops truncatus truncatus)

Accurate estimates of abundance are critical to species management and conservation. Common bottlenose dolphins (Tursiops truncatus truncatus) inhabiting the Indian River Lagoon (IRL) estuarine system along the east coast of Florida are impacted by anthropogenic activities and have had multiple unexplained mortality events, necessitating precise estimates of demographic and abundance parameters to implement management strategies. Mark-recapture methodology following a Robust Design survey was used to estimate abundance, adult survival, and temporary emigration for the IRL estuarine system stock of bottlenose dolphins. Models included a parameter (time since first capture) to assess evidence for transient individuals. Boat-based photo-identification surveys (n = 135) were conducted along predetermined contour and transect lines throughout the entire IRL (2016-2017). The best fitting model included the "transient" parameter to survival, allowed survival to vary by primary period, detection to vary by secondary session, and did not allow temporary emigration. Dolphin abundance ranged from 981 (95% CI: 882-1,090) in winter to 1,078 (95% CI: 968-1,201) in summer with a mean of 1,032 (95% CI: 969 -1,098). Model averaged seasonal survival rate for marked residents ranged from 0.85-1.00. Capture probability ranged from 0.20 to 0.42 during secondary sessions and transient rate from 0.06 to 0.07. This study represents the first Robust design mark-recapture survey effort to estimate abundance for IRL dolphins and provides parameter estimates to optimize sampling design of future studies. Transients included individuals with home ranges extending north of the IRL requiring further assessment of stock delineation. Results were remarkably similar to prior abundance estimates resulting from line-transect aerial surveys and were consistent with a stable population. Data will enable managers to evaluate the impact of fisheries-related takes as well as enable future comparisons of demographic parameters for a dolphin population that continues to sustain large scale mortality events and anthropogenic impacts.

ecology↗

bioRxiv2018

Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry

To define the cell populations in rheumatoid arthritis (RA) driving joint inflammation, we applied single-cell RNA-seq (scRNA-seq), mass cytometry, bulk RNA-seq, and flow cytometry to sorted T cells, B cells, monocytes, and fibroblasts from 51 synovial tissue RA and osteoarthritis (OA) patient samples. Utilizing an integrated computational strategy based on canonical correlation analysis to 5,452 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics together revealed cell states expanded in RA synovia: THY1+HLAhigh sublining fibroblasts (OR=33.8), IL1B+ pro-inflammatory monocytes (OR=7.8), CD11c+T-bet+ autoimmune-associated B cells (OR=5.7), and PD-1+Tph/Tfh (OR=3.0). We also defined CD8+ T cell subsets characterized by GZMK+, GZMB+, and GNLY+ expression. Using bulk and single-cell data, we mapped inflammatory mediators to source cell populations, for example attributing IL6 production to THY1+HLAhigh fibroblasts and naive B cells, and IL1B to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

immunology↗