Browsing by Author "Murphy, Quiyana M."

Now showing 1 - 2 of 2
  • Thumbnail Image
    TCDD and CH223191 alter T cell balance but fail to induce anti-inflammatory response in adult lupus mice
    Gutierrez, Fernando; Murphy, Quiyana M.; Swartwout, Brianna K.; Read, Kaitlin A.; Edwards, Michael R.; Abdelhamid, Leila; Cabana-Puig, Xavier; Testerman, James C.; Xu, Tian; Lu, Ran; Amin, Pavly; Cecere, Thomas E.; Reilly, Christopher M.; Oestreich, Kenneth J.; Ciupe, Stanca M.; Luo, Xin M. (The American Association of Immunologists, 2024-02-14)
    Aryl hydrocarbon receptor (AhR) responds to endogenous and exogenous ligands as a cytosolic receptor, transcription factor, and E3 ubiquitin ligase. Several studies support an anti-inflammatory effect of AhR activation. However, exposure to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early stages of development results in an autoimmune phenotype and exacerbates lupus. The effects of TCDD on lupus in adults with pre-existing autoimmunity have not been described. We present novel evidence that AhR stimulation by TCDD alters T cell responses but fails to impact lupus-like disease using an adult mouse model. Interestingly, AhR antagonist CH223191 also changed T cell balance in our model. We next developed a conceptual framework for identifying cellular and molecular factors that contribute to physiological outcomes in lupus and created models that describe cytokine dynamics that were fed into a system of differential equations to predict the kinetics of T follicular helper (Tfh) and regulatory T (Treg) cell populations. The model predicted that Tfh cells expanded to larger values following TCDD exposure compared with vehicle and CH223191. Following the initial elevation, both Tfh and Treg cell populations continuously decayed over time. A function based on the ratio of predicted Treg/Tfh cells showed that Treg cells exceed Tfh cells in all groups, with TCDD and CH223191 showing lower Treg/Tfh cell ratios than the vehicle and that the ratio is relatively constant over time. We conclude that AhR ligands did not induce an anti-inflammatory response to attenuate autoimmunity in adult lupus mice. This study challenges the dogma that TCDD supports an immunosuppressive phenotype.
  • Thumbnail Image
    Understanding Neutrophil Dynamics during COVID-19 Infection
    Murphy, Quiyana M.; Ciupe, Stanca M. (MDPI, 2023-02-13)
    Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in varied clinical outcomes, with virus-induced chronic inflammation and tissue injury being associated with enhanced disease pathogenesis. To determine the role of tissue damage on immune populations recruitment and function, a mathematical model of innate immunity following SARS-CoV-2 infection has been proposed. The model was fitted to published longitudinal immune marker data from patients with mild and severe COVID-19 disease and key parameters were estimated for each clinical outcome. Analytical, bifurcation, and numerical investigations were conducted to determine the effect of parameters and initial conditions on long-term dynamics. The results were used to suggest changes needed to achieve immune resolution.