Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective T H 17 responses.

Autor: Sun H; Center for Immunology and Autoimmune Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School of The University of Texas Health Science Center at Houston, Houston, Tex; Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Tex., Knight JM; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Tex., Li YD; Center for Immunology and Autoimmune Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School of The University of Texas Health Science Center at Houston, Houston, Tex; Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Tex., Ashoori F; Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Tex., Citardi MJ; Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Tex., Yao WC; Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Tex., Corry DB; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Tex; Department of Medicine, Baylor College of Medicine, Houston, Tex; Biology of Inflammation Center and Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Tex., Luong AU; Center for Immunology and Autoimmune Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School of The University of Texas Health Science Center at Houston, Houston, Tex; Department of Otorhinolaryngology-Head and Neck Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Tex. Electronic address: amber.u.luong@uth.tmc.edu.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2024 Nov; Vol. 154 (5), pp. 1169-1179. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1016/j.jaci.2024.06.022
Abstrakt: Background: In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS.
Objective: We sought to identify the molecular etiology of the downregulated expression of HTN1.
Methods: We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of T H 17/T H 22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls.
Results: We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for T H 17/T H 22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating T H 17 cell abundance was normal.
Conclusions: Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for T H 17/T H 22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.
Competing Interests: Disclosure statement This work was supported by National Institutes of Health grants R01HL117181 (D.B.C.), HL140398 (D.B.C.), R01AI135803 (D.B.C.), and R01AI135803 (D.B.C.) and Department of Veterans AffairsBiomedical Laboratory Research and Development Merit Review Award I01BX004828 (D.B.C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health or the Veterans Administration Office of Research and Development. This project was further supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the CPRIT Core Facility Support Award (CPRIT-RP180672), and the National Institutes of Health (CA125123 and RR024574). Disclosure of potential conflict of interest: A. U. Luong owns stock in Aerin Medical (Mountain View, Calif) and serves as a consultant for GlaxoSmithKline (Brentford, United Kingdom), Lyra Therapeutics (Watertown, Mass), Maxwell Biosciences (Austin, Texas), Medtronic (Dublin, Ireland), NeuroENT (Galway, Ireland), Sanofi (Paris, France), SoundHealth (San Francisco, Calif), and Stryker (Kalamazoo, Mich). D. B. Corry owns stock options in Maxwell Biosciences (Austin, Texas). M. J. Citardi serves as a consultant for 3D Matrix (Newton, Mass), Acclarent (Irvine, Calif), LynxMD (Palo Alto, Calif), MicroGenDx (Lubbock, Texas), and NeuroENT (Galway, Ireland). W. C. Yao is a consultant for Acclarent (Irvine, Calif), Aerin Medical (Mountain View, Calif), and Medtronic (Minneapolis, Minn) and is on the Speaker’s Bureau for Optinose Inc (Yardley, Pa).
(Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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