title: Roles of Epithelial Cell-Derived Type 2-Initiating Cytokines in Experimental Allergic Conjunctivitis.
abstract: OBJECTIVE
  To clarify the possible involvement of the type 2-initiating cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) in the pathophysiology of allergic conjunctivitis, we evaluated ragweed (RW)-induced experimental allergic conjunctivitis (EAC) models by using IL-25 knockout (KO), IL-33 KO, and TSLP receptor (TSLPR) KO mice.
  
  
  METHODS
  Interleukin-25 KO, IL-33 KO, TSLPR KO, and BALB/c wild-type mice were sensitized twice with RW in alum and then challenged with RW in eye drops. Clinical scores and eosinophil infiltration were evaluated. Expression levels of serum immunoglobulin E (IgE) and cytokines in the conjunctival tissues were quantified and immunohistochemical analysis was carried out.
  
  
  RESULTS
  Significant reductions in clinical scores and numbers of infiltrating eosinophils were observed in the RW-EAC model using IL-33 KO mice. There were no significant differences in clinical scores and numbers of infiltrating eosinophils among IL-25KO, TSLPR KO, and wild-type mice. Serum IgE concentration was upregulated after RW challenges, and there were no differences among the mouse genotypes. Expression levels of of il4, il5, il13, and ccl5 mRNA were diminished in the conjunctivae of the RW-EAC model using IL-33 KO mice compared to those in wild-type mice. Interleukin-33 expression was upregulated as early as 1 hour after RW eye-drop challenge. The number of infiltrating basophils in the conjunctivae of the RW-EAC model using IL-33 KO mice was diminished compared to that in wild-type mice.
  
  
  CONCLUSIONS
  Among the type 2-initiating cytokines, IL-33 may play a major role in conjunctival inflammation in an RW-EAC model.
authors.affiliation: Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan 2Frontier Research Initiative, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Asada
authors.affiliation: Frontier Research Initiative, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Department of Ophthalmology, Kochi University School of Medicine, Nangoku, Japan.
authors.forename: Waka
authors.initials: W
authors.lastname: Ishida
authors.affiliation: Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Hori
authors.affiliation: Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Jobu
authors.initials: J
authors.lastname: Sugita
authors.affiliation: Animal Research Center, Tokyo Medical University, Tokyo, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.affiliation: Department of Ophthalmology, Kochi University School of Medicine, Nangoku, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Ophthalmology, Kochi University School of Medicine, Nangoku, Japan.
authors.forename: Atsuki
authors.initials: A
authors.lastname: Fukushima
authors.affiliation: Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan 6Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.affiliation: Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.affiliation: Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ebihara
authors.affiliation: Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003228:Conjunctiva / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics*; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C506535:Il33 protein, mouse; D020381:Interleukin-17; D000067596:Interleukin-33; D007378:Interleukins; C442281:Mydgf protein, mouse; D007073:Immunoglobulin E; D012313:RNA; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse