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T Cell Resistance: On the Mechanisms of T Cell Non-activation.
Immune Netw
December 2024
The Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, United Kingdom.
Immunological tolerance is a fundamental arm of any functioning immune system. Not only does tolerance mitigate collateral damage from host immune responses, but in doing so permits a robust response sufficient to clear infection as necessary. Yet, despite occupying such a cornerstone, research aiming to unravel the intricacies of tolerance induction is mired by interchangeable and often misused terminologies, with markers and mechanistic pathways that beg the question of redundancy.
View Article and Find Full Text PDFGenetically Encoded Biosensors for Constrained Biological Functions in Probiotic Nissle.
ACS Synth Biol
January 2025
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian 361102, China.
The probiotic Nissle (EcN) is an exceptional strain that has attracted significant attention not only for its clinical efficacy in the treatment and prevention of gastrointestinal disorders but also as a burgeoning microbial chassis for living therapeutic applications. However, there is an immediate necessity to develop conditional expression systems that confine the activity of EcN specifically in the gastrointestinal tract, to avoid influencing the environment. Here, we constructed two genetically encoded interchangeable sensors responsive to body temperature at 37 °C, and small molecules such as protocatechuic acid (PCA), a metabolite found in green tea.
View Article and Find Full Text PDFProstanoid signaling in retinal cells elicits inflammatory responses relevant to early-stage diabetic retinopathy.
J Neuroinflammation
December 2024
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Inflammation is a critical driver of the early stages of diabetic retinopathy (DR) and offers an opportunity for therapeutic intervention before irreversible damage and vision loss associated with later stages of DR ensue. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown mixed efficacy in slowing early DR progression, notably including severe adverse side effects likely due to their nonselective inhibition of all downstream signaling intermediates. In this study, we investigated the role of prostanoids, the downstream signaling lipids whose production is inhibited by NSAIDs, in promoting inflammation relevant to early-stage DR in two human retinal cell types: Müller glia and retinal microvascular endothelial cells.
View Article and Find Full Text PDFCell-Based Assays to Detect Innate Immune Response Modulating Impurities: Application to Biosimilar Insulin.
AAPS J
December 2024
Laboratory of Immunology, Office of Pharmaceutical Quality Research Division-IV, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
Characterizing and mitigating factors that impact product immunogenicity can aid in risk assessment and/or managing risk following manufacturing changes. For follow-on products that have the same indication, patient population, and active product ingredient, the residual immunogenicity risk resides predominantly on differences in product and process related impurities. Characterizing differences in innate immune modulating impurities (IIRMI), which could act as adjuvants by activating local antigen presenting cells (APCs), can inform the immunogenicity risk assessment potentially reducing the need for clinical trials.
View Article and Find Full Text PDFInterplay between β-propeller subunits WDR26 and muskelin regulates the CTLH E3 ligase supramolecular complex.
Commun Biol
December 2024
Robarts Research Institute, University of Western Ontario, London, ON, N6A 5B7, Canada.
The Pro/N-degron recognizing C-terminal to LisH (CTLH) complex is an E3 ligase of emerging interest in the developmental biology field and for targeted protein degradation (TPD) modalities. The human CTLH complex forms distinct supramolecular ring-shaped structures dependent on the multimerization of WDR26 or muskelin β-propeller proteins. Here, we find that, in HeLa cells, CTLH complex E3 ligase activity is dictated by an interplay between WDR26 and muskelin in tandem with muskelin autoregulation.
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