دورية أكاديمية
أعرض في EDS

Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype.

التفاصيل البيبلوغرافية
العنوان: Increased Production of LIGHT by T Cells in Eosinophilic Esophagitis Promotes Differentiation of Esophageal Fibroblasts Toward an Inflammatory Phenotype.
المؤلفون: Manresa MC; Department of Pediatrics, University of California, San Diego, San Diego; Division of Allergy Immunology; La Jolla Institute for Immunology, La Jolla, California., Chiang AWT; Department of Pediatrics, University of California, San Diego, San Diego; Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, San Diego, California., Kurten RC; Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas., Dohil R; Rady Children's Hospital, San Diego., Brickner H; Department of Medicine, University of California, San Diego, San Diego, California., Dohil L; Department of Pediatrics, University of California, San Diego, San Diego., Herro R; Cincinnati Children's Hospital Medical Center, Immunobiology Division, Cincinnati, Ohio., Akuthota P; Division of Gastroenterology, Department of Pediatrics, University of California, San Diego; Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San Diego, La Jolla, California., Lewis NE; Department of Pediatrics, University of California, San Diego, San Diego; Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, San Diego, California; Department of Bioengineering, University of California, San Diego, San Diego, California., Croft M; La Jolla Institute for Immunology, La Jolla, California; Division of Gastroenterology, Department of Pediatrics, University of California, San Diego., Aceves SS; Department of Pediatrics, University of California, San Diego, San Diego; Division of Allergy Immunology; Rady Children's Hospital, San Diego; Division of Gastroenterology, Department of Pediatrics, University of California, San Diego. Electronic address: saceves@health.ucsd.edu.
المصدر: Gastroenterology [Gastroenterology] 2020 Nov; Vol. 159 (5), pp. 1778-1792.e13. Date of Electronic Publication: 2020 Jul 23.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: W.B. Saunders Country of Publication: United States NLM ID: 0374630 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0012 (Electronic) Linking ISSN: 00165085 NLM ISO Abbreviation: Gastroenterology Subsets: MEDLINE
أسماء مطبوعة: Publication: Philadelphia, PA : W.B. Saunders
Original Publication: Baltimore.
مواضيع طبية MeSH: Cell Differentiation* , Paracrine Communication*, Eosinophilic Esophagitis/*metabolism , Esophagus/*metabolism , Fibroblasts/*metabolism , Inflammation Mediators/*metabolism , T-Lymphocytes/*metabolism , Tumor Necrosis Factor Ligand Superfamily Member 14/*metabolism, Adolescent ; Case-Control Studies ; Cells, Cultured ; Child ; Child, Preschool ; Eosinophilic Esophagitis/immunology ; Eosinophilic Esophagitis/pathology ; Esophagus/immunology ; Esophagus/pathology ; Female ; Fibroblasts/immunology ; Fibroblasts/pathology ; Humans ; Intercellular Adhesion Molecule-1/metabolism ; Male ; Phenotype ; Receptors, Tumor Necrosis Factor, Member 14/metabolism ; Signal Transduction ; T-Lymphocytes/immunology ; Tumor Necrosis Factor Ligand Superfamily Member 14/genetics ; Up-Regulation
مستخلص: Background & Aims: Eosinophilic esophagitis (EoE) is an antigen-mediated eosinophilic disease of the esophagus that involves fibroblast activation and progression to fibrostenosis. Cytokines produced by T-helper type 2 cells and transforming growth factor beta 1 (TGFβ1) contribute to the development of EoE, but other cytokines involved in pathogenesis are unknown. We investigate the effects of tumor necrosis factor superfamily member 14 (TNFSF14, also called LIGHT) on fibroblasts in EoE.
Methods: We analyzed publicly available esophageal CD3 + T-cell single-cell sequencing data for expression of LIGHT. Esophageal tissues were obtained from pediatric patients with EoE or control individuals and analyzed by immunostaining. Human primary esophageal fibroblasts were isolated from esophageal biopsy samples of healthy donors or patients with active EoE. Fibroblasts were cultured; incubated with TGFβ1 and/or LIGHT; and analyzed by RNA sequencing, flow cytometry, immunoblots, immunofluorescence, or reverse transcription polymerase chain reaction. Eosinophils were purified from peripheral blood of healthy donors, incubated with interleukin 5, cocultured with fibroblasts, and analyzed by immunohistochemistry.
Results: LIGHT was up-regulated in the esophageal tissues from patients with EoE, compared with control individuals, and expressed by several T-cell populations, including T-helper type 2 cells. TNF receptor superfamily member 14 (TNFRSF14, also called HVEM) and lymphotoxin beta receptor are receptors for LIGHT that were expressed by fibroblasts from healthy donors or patients with active EoE. Stimulation of esophageal fibroblasts with LIGHT induced inflammatory gene transcription, whereas stimulation with TGFβ1 induced transcription of genes associated with a myofibroblast phenotype. Stimulation of fibroblasts with TGFβ1 increased expression of HVEM; subsequent stimulation with LIGHT resulted in their differentiation into cells that express markers of myofibroblasts and inflammatory chemokines and cytokines. Eosinophils tethered to esophageal fibroblasts after LIGHT stimulation via intercellular adhesion molecule-1.
Conclusions: T cells in esophageal tissues from patients with EoE express increased levels of LIGHT compared with control individuals, which induces differentiation of fibroblasts into cells with inflammatory characteristics. TGFβ1 increases fibroblast expression of HVEM, a receptor for LIGHT. LIGHT mediates interactions between esophageal fibroblasts and eosinophils via ICAM1. This pathway might be targeted for the treatment of EoE.
(Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)
References: Bioinformatics. 2015 Jan 15;31(2):166-9. (PMID: 25260700)
Nat Immunol. 2019 Jul;20(7):928-942. (PMID: 31061532)
Dig Dis. 2014;32(1-2):15-21. (PMID: 24603375)
Allergy. 2018 Jul;73(7):1415-1424. (PMID: 29315623)
Mediators Inflamm. 2014;2014:136463. (PMID: 24782592)
J Invest Dermatol. 2015 Aug;135(8):2109-2118. (PMID: 25789702)
J Allergy Clin Immunol. 2005 Oct;116(4):796-804. (PMID: 16210053)
Eur J Med Res. 2009 Apr 16;14(4):147-56. (PMID: 19380287)
J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):200-9. (PMID: 26727658)
J Clin Invest. 2019 Apr 8;129(5):2014-2028. (PMID: 30958799)
J Immunol. 2000 Apr 15;164(8):4105-10. (PMID: 10754304)
Am J Gastroenterol. 2015 May;110(5):626-32. (PMID: 25267327)
Gastroenterology. 1999 Sep;117(3):546-56. (PMID: 10464130)
Cancer Cell. 2016 Mar 14;29(3):285-296. (PMID: 26977880)
Front Immunol. 2018 Nov 22;9:2624. (PMID: 30524424)
J Immunol. 2015 Sep 1;195(5):2429-41. (PMID: 26209626)
J Allergy Clin Immunol. 2016 Sep;138(3):791-800.e4. (PMID: 27212082)
Commun Biol. 2020 Apr 23;3(1):188. (PMID: 32327715)
Front Immunol. 2018 Mar 19;9:576. (PMID: 29616048)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nat Med. 2011 May;17(5):596-603. (PMID: 21499267)
J Immunol. 2004 Jul 1;173(1):251-8. (PMID: 15210782)
J Biol Chem. 2003 Sep 19;278(38):36763-76. (PMID: 12815062)
Mucosal Immunol. 2020 Jan;13(1):110-117. (PMID: 31636346)
PLoS One. 2015 Dec 14;10(12):e0144651. (PMID: 26656423)
Ann Allergy Asthma Immunol. 2014 May;112(5):397-403. (PMID: 24566295)
Cell. 2018 Oct 4;175(2):372-386.e17. (PMID: 30270042)
Dig Dis Sci. 2013 Jun;58(6):1497-506. (PMID: 23456499)
Sci Rep. 2019 Feb 28;9(1):3172. (PMID: 30816272)
J Allergy Clin Immunol. 2019 Jul;144(1):171-182. (PMID: 30578874)
Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):E5688-96. (PMID: 25512551)
Am J Physiol Regul Integr Comp Physiol. 2014 Dec 15;307(12):R1369-80. (PMID: 25298511)
J Allergy Clin Immunol. 2014 Nov;134(5):1100-1107.e4. (PMID: 24835503)
Bioinformatics. 2009 May 1;25(9):1105-11. (PMID: 19289445)
J Exp Med. 2018 Feb 5;215(2):415-422. (PMID: 29339444)
Allergy. 2012 Oct;67(10):1299-307. (PMID: 22913672)
J Immunol. 2019 Jul 15;203(2):329-337. (PMID: 31175163)
J Immunol. 2005 Jan 15;174(2):646-53. (PMID: 15634882)
Nat Commun. 2019 Feb 8;10(1):650. (PMID: 30737373)
Front Med (Lausanne). 2017 Aug 07;4:128. (PMID: 28831387)
J Leukoc Biol. 2018 Jul;104(1):31-40. (PMID: 29377264)
J Pediatr Gastroenterol Nutr. 2014 Jul;59(1):10-6. (PMID: 24590208)
Nat Commun. 2016 Dec 16;7:13696. (PMID: 27982078)
Immunology. 2010 Nov;131(3):357-70. (PMID: 20518822)
J Pediatr Gastroenterol Nutr. 2015 Aug;61(2):194-9. (PMID: 25539192)
J Allergy Clin Immunol. 2010 Dec;126(6):1198-204.e4. (PMID: 21047675)
Cancer Res. 2015 Dec 15;75(24):5248-59. (PMID: 26631268)
Bioinformatics. 2011 Mar 15;27(6):863-4. (PMID: 21278185)
Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: 19505943)
J Allergy Clin Immunol. 2015 Sep;136(3):757-68. (PMID: 25680454)
Sci Transl Med. 2013 Jul 24;5(195):195ra94. (PMID: 23884466)
J Immunol. 2001 Dec 1;167(11):6330-7. (PMID: 11714797)
معلومات مُعتمدة: K24 AI135034 United States AI NIAID NIH HHS; R01 AI092135 United States AI NIAID NIH HHS; R01 DK114457 United States DK NIDDK NIH HHS; R35 GM119850 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Eosinophilia; Fibrogenesis; Fibrosis; ICAM1; Immune Regulation
المشرفين على المادة: 0 (ICAM1 protein, human)
0 (Inflammation Mediators)
0 (Receptors, Tumor Necrosis Factor, Member 14)
0 (TNFRSF14 protein, human)
0 (TNFSF14 protein, human)
0 (Tumor Necrosis Factor Ligand Superfamily Member 14)
126547-89-5 (Intercellular Adhesion Molecule-1)
تواريخ الأحداث: Date Created: 20200727 Date Completed: 20210412 Latest Revision: 20240330
رمز التحديث: 20240330
مُعرف محوري في PubMed: PMC7726704
DOI: 10.1053/j.gastro.2020.07.035
PMID: 32712105
قاعدة البيانات: MEDLINE
الوصف
تدمد:1528-0012
DOI:10.1053/j.gastro.2020.07.035