Browsing by Author "Haouili, Maya"

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    FOXP3 exon 2 controls Treg stability and autoimmunity
    (American Association for the Advancement of Science, 2022) Du, Jianguang; Wang, Qun; Yang, Shuangshuang; Chen, Si; Fu, Yongyao; Spath, Sabine; Domeier, Phillip; Hagin, David; Anover-Sombke, Stephanie; Haouili, Maya; Liu, Sheng; Wan, Jun; Han, Lei; Liu, Juli; Yang, Lei; Sangani, Neel; Li, Yujing; Lu, Xiongbin; Janga, Sarath Chandra; Kaplan, Mark H.; Torgerson, Troy R.; Ziegler, Steven F.; Zhou, Baohua; Pediatrics, School of Medicine
    Differing from the mouse Foxp3 gene that encodes only one protein product, human FOXP3 encodes two major isoforms through alternative splicing-a longer isoform (FOXP3 FL) containing all the coding exons and a shorter isoform lacking the amino acids encoded by exon 2 (FOXP3 ΔE2). The two isoforms are naturally expressed in humans, yet their differences in controlling regulatory T cell phenotype and functionality remain unclear. In this study, we show that patients expressing only the shorter isoform fail to maintain self-tolerance and develop immunodeficiency, polyendocrinopathy, and enteropathy X-linked (IPEX) syndrome. Mice with Foxp3 exon 2 deletion have excessive follicular helper T (TFH) and germinal center B (GC B) cell responses, and develop systemic autoimmune disease with anti-dsDNA and antinuclear autoantibody production, as well as immune complex glomerulonephritis. Despite having normal suppressive function in in vitro assays, regulatory T cells expressing FOXP3 ΔE2 are unstable and sufficient to induce autoimmunity when transferred into Tcrb-deficient mice. Mechanistically, the FOXP3 ΔE2 isoform allows increased expression of selected cytokines, but decreased expression of a set of positive regulators of Foxp3 without altered binding to these gene loci. These findings uncover indispensable functions of the FOXP3 exon 2 region, highlighting a role in regulating a transcriptional program that maintains Treg stability and immune homeostasis.
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    The Sound of Safety: DIVOT (Doppler Imaging for Vascular Orientation in Thoracic Procedures) Protocol
    (CINQUILL Medical, 2025-04-15) Fraser, Amy; Brenner, Daniel S.; Coghlan, Matthew; Andrade, Heather; Haouili, Maya; Carlos, William Graham; Jackson, Edwin; Emergency Medicine, School of Medicine
    Each year, more than 200,000 thoracentesis and percutaneous chest tube thoracostomy procedures are performed in the United States [1-4]. In both procedures, the initial step involves advancing a needle over the superior aspect of the rib into the intercostal space to access the pleural cavity. Traditional teaching suggests that this technique avoids the neurovascular bundle, which is typically shielded by the inferior border of the rib. However, this technique does not guarantee safety. Computed tomography studies have shown that the intercostal arteries (ICAs) are highly tortuous, with positions that can vary significantly within the intercostal space [5-7]. This variability can lead to ICA laceration even with an optimal traditional technique [8-9]. Significant hemorrhage into the pleural space may initially go unnoticed but can progress to hemorrhagic shock or even tension hemothorax physiology [10-12]. Improved procedural guidance is needed to enhance safety and achieve the goal of zero patient harm. We propose the DIVOT (Doppler Imaging for Vascular Orientation in Thoracic procedures) protocol using a combination of high-frequency linear ultrasound, color, and Power Doppler (PD) to identify an ICA and its collaterals before needle insertion. This can reduce the risk of accidental vascular injury during thoracentesis or percutaneous chest tube thoracostomy.