دورية أكاديمية
أعرض في EDS

Lymphotoxin beta receptor signaling directly controls airway smooth muscle deregulation and asthmatic lung dysfunction.

التفاصيل البيبلوغرافية
العنوان: Lymphotoxin beta receptor signaling directly controls airway smooth muscle deregulation and asthmatic lung dysfunction.
المؤلفون: Miki H; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif., Kiosses WB; Microscopy Core, La Jolla Institute for Immunology, La Jolla, Calif., Manresa MC; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif., Gupta RK; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif., Sethi GS; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif., Herro R; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif., Da Silva Antunes R; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif., Dutta P; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif., Miller M; Department of Medicine, University of California-San Diego, San Diego, Calif., Fung K; Bioinformatics Core, La Jolla Institute for Immunology, La Jolla, Calif., Chawla A; Bioinformatics Core, La Jolla Institute for Immunology, La Jolla, Calif., Dobaczewska K; Microscopy Core, La Jolla Institute for Immunology, La Jolla, Calif., Ay F; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif., Broide DH; Department of Medicine, University of California-San Diego, San Diego, Calif., Tumanov AV; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center, San Antonio, Tex., Croft M; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif; Department of Medicine, University of California-San Diego, San Diego, Calif. Electronic address: mick@lji.org.
المصدر: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2023 Apr; Vol. 151 (4), pp. 976-990.e5. Date of Electronic Publication: 2022 Dec 05.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Mosby Country of Publication: United States NLM ID: 1275002 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6825 (Electronic) Linking ISSN: 00916749 NLM ISO Abbreviation: J Allergy Clin Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: St Louis, Mosby.
مواضيع طبية MeSH: Receptors, Tumor Necrosis Factor, Member 14* , Asthma*/pathology, Humans ; Mice ; Animals ; Lymphotoxin beta Receptor/genetics ; Muscle, Smooth ; Myocytes, Smooth Muscle/pathology ; Mice, Knockout ; Allergens ; Lung/pathology
مستخلص: Background: Dysregulation of airway smooth muscle cells (ASM) is central to the severity of asthma. Which molecules dominantly control ASM in asthma is unclear. High levels of the cytokine LIGHT (aka TNFSF14) have been linked to asthma severity and lower baseline predicted FEV 1 percentage, implying that signals through its receptors might directly control ASM dysfunction.
Objective: Our study sought to determine whether signaling via lymphotoxin beta receptor (LTβR) or herpesvirus entry mediator from LIGHT dominantly drives ASM hyperreactivity induced by allergen.
Methods: Conditional knockout mice deficient for LTβR or herpesvirus entry mediator in smooth muscle cells were used to determine their role in ASM deregulation and airway hyperresponsiveness (AHR) in vivo. Human ASM were used to study signals induced by LTβR.
Results: LTβR was strongly expressed in ASM from normal and asthmatic subjects compared to several other receptors implicated in smooth muscle deregulation. Correspondingly, conditional deletion of LTβR only in smooth muscle cells in smMHC Cre LTβR fl/fl mice minimized changes in their numbers and mass as well as AHR induced by house dust mite allergen in a model of severe asthma. Intratracheal LIGHT administration independently induced ASM hypertrophy and AHR in vivo dependent on direct LTβR signals to ASM. LIGHT promoted contractility, hypertrophy, and hyperplasia of human ASM in vitro. Distinguishing LTβR from the receptors for IL-13, TNF, and IL-17, which have also been implicated in smooth muscle dysregulation, LIGHT promoted NF-κB-inducing kinase-dependent noncanonical nuclear factor kappa-light-chain enhancer of activated B cells in ASM in vitro, leading to sustained accumulation of F-actin, phosphorylation of myosin light chain kinase, and contractile activity.
Conclusions: LTβR signals directly and dominantly drive airway smooth muscle hyperresponsiveness relevant for pathogenesis of airway remodeling in severe asthma.
(Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R21 AI111000 United States AI NIAID NIH HHS; U19 AI070535 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: AHR; LIGHT; LTβR; TNF superfamily; TNFSF14; airway smooth muscle; asthma; contractility; noncanonical NF-κB
المشرفين على المادة: 0 (Receptors, Tumor Necrosis Factor, Member 14)
0 (Lymphotoxin beta Receptor)
0 (Allergens)
تواريخ الأحداث: Date Created: 20221206 Date Completed: 20230411 Latest Revision: 20240402
رمز التحديث: 20240402
مُعرف محوري في PubMed: PMC10081945
DOI: 10.1016/j.jaci.2022.11.016
PMID: 36473503
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-6825
DOI:10.1016/j.jaci.2022.11.016