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Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice
Affiliation:1. Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan;2. Department of Ophthalmology, Juntendo University Urayasu Hospital, Urayasu, Chiba, 279-0021, Japan;3. Department of Ophthalmology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan;4. Laboratory of Cell Biotechnology, Biotechnology Research Center, The University of Tokyo, Tokyo, 113-8657, Japan;5. Department of Science of Allergy and Inflammation, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan;6. Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan;7. Department of Immunological Diagnosis, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan;1. Center for Translational Ocular Immunology, USA;2. Cornea Service, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine Boston, MA, USA;3. Department of Ophthalmology, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA;1. Department of Environmental Health Sciences, Yale School of Public Health, Yale University, 60 College Street, New Haven, CT, USA;2. Department of Cellular & Molecular Physiology, Yale School of Medicine, Yale University, New Haven, CT, USA;3. Bioinformatics Support Program, Cushing/Whitney Medical Library, Yale School of Medicine, New Haven, CT, USA;4. Department of Medicine, Yale University School of Medicine, New Haven, CT, USA;5. Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA;6. Department of Ophthalmology & Visual Science, Yale School of Medicine, New Haven, CT, USA;7. Department of Pathology, Anschutz School of Medicine, University of Colorado, Aurora, CO, USA;8. Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA;9. Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA;1. Brookline, MA, USA;2. TFOS, Boston, MA, USA;3. Department of Ophthalmology, Antioquia Ophthalmology Clinic-Clofan, Medellin, Antioquia, Colombia;4. Department of Ophthalmology and Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas – UNICAMP, São Paulo, Brazil;5. Ocular Surface Center and Department of Ophthalmology, Sacco Hospital, Milan University, Milan, Italy;6. Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, Auckland, New Zealand;7. Ophthalmology Department, Lebanese University, Beirut, Lebanon;8. Earlam and Christopher Optometrists and Contact Lens Specialists, Taunton, UK;9. Department of Ophthalmology and Visual Sciences, Federal University of São Paulo/Paulista School of Medicine, São Paulo, Brazil;10. University of Cape Town, Cape Town, South Africa;11. Sankara Nethralya, Chennai, Tamil Nadu, India;12. Cornea and Refractive Surgery, Beirut Eye and ENT Specialist Hospital, Ophthalmology Department, Lebanese University, Beirut, Lebanon, and Mediclinic Dubai Mall, Dubai, United Arab Emirates;13. Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan;14. Department of Optometry and Visual Science, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana;15. Cabinet Ophthalmologie, Alger Centre, Algiers, Algeria;p. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA;q. Ophthalmology Department, Saint Joseph University, Beirut, Lebanon;r. Institute of Ophthalmology, Conde de Valenciana, National Autonomous University of Mexico, UNAM, Mexico City, Mexico;s. Department of Optometry, School of Health Sciences at the College of Health Sciences, Makerere University, Kampala, Uganda;t. University of Alexandria, Alexandria, Egypt;u. Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan;v. School of Optometry and Vision Science, UNSW Sydney, Sydney, Australia;w. Section of Academic Ophthalmology, King''s College London, London, UK, and Departments of Ophthalmology and Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands;x. Department of Specialized, Experimental, and Diagnostic Medicine, University of Bologna, Bologna, Italy
Abstract:PurposeWe aimed to clarify the role of particulate allergen exposure to the conjunctiva in the development of allergic conjunctivitis.MethodsWe administered ragweed pollen suspension, pollen extract, pollen shell, particulate air pollutants, and their combinations to the mouse conjunctiva five days a week without prior sensitization. Clinical signs were scored. Histological changes, cellular infiltrations, mRNA expressions, lymph node cell recall responses, and serum immunoglobulin levels were assessed. Immune cell-depleting antibodies and ST2 knockout mice were used to investigate the cellular and molecular requirements.ResultsPollen suspension, but not the extract or shell alone, induced robust eosinophilic conjunctivitis, accompanied by a proliferative response of epithelial cells. A combination of pollen extract and shell completely restored eosinophil accumulation. In addition, eosinophilic conjunctivitis was induced by a mixture of particulate air pollutants and pollen extract. Mechanistically, eosinophil accumulation was ameliorated by deficiency of the IL-33 receptor ST2 and abolished by depleting CD4+ T cells. Pollen shells, but not the extract, induced IL-33 release from conjunctival epithelial cells in vivo.ConclusionsOur results indicate the non-redundant roles for the allergens’ particulate properties and soluble factors in the development of allergic conjunctivitis.
Keywords:Allergic conjunctivitis  CD4+ST2+ T cells  IL-33  Pollen  Shell  CRISPR"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0040"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  clustered regularly interspaced short palindromic repeats  DAPI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0050"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  4′,6-diamidino-2-phenylindole  ELISA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0060"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  enzyme-linked immunosorbent assay  IL"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0070"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  interleukin  PBS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0080"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  phosphate buffered saline  Th"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0090"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  helper T  Tpath2"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0100"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  pathogenic type 2 helper T  TSLP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0110"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  thymic stromal lymphopoietin
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