title: Homeostatic control of conjunctival mucosal goblet cells by NKT-derived IL-13.
abstract: Although the effects of the interleukin 13 (IL-13) on goblet cell (GC) hyperplasia have been studied in the gut and respiratory tracts, its effect on regulating conjunctival GC has not been explored. The purpose of this study was to determine the major IL-13-producing cell type and the role of IL-13 in GC homeostasis in normal murine conjunctiva. Using isolating techniques, we identified natural killer (NK)/natural killer T (NKT) cells as the main producers of IL-13. We also observed that IL-13 knockout (KO) and signal transducer and activator of transcription 6 knockout (STAT6KO) mice had a lower number of periodic acid Schiff (PAS)+GCs. We observed that desiccating stress (DS) decreases NK population, GCs, and IL-13, whereas it increases interferon-γ (IFN-γ) mRNA in conjunctiva. Cyclosporine A treatment during DS maintained the number of NK/NKT cells in the conjunctiva, increased IL-13 mRNA in NK+ cells, and decreased IFN-γ and IL-17A mRNA transcripts in NK+ and NK- populations. C57BL/6 mice chronically depleted of NK/NKT cells, as well as NKT cell-deficient RAG1KO and CD1dKO mice, had fewer filled GCs than their wild-type counterparts. NK depletion in CD1dKO mice had no further effect on the number of PAS+ cells. Taken together, these findings indicate that NKT cells are major sources of IL-13 in the conjunctival mucosa that regulates GC homeostasis.
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA. cintiadp@bcm.tmc.edu
authors.forename: C S
authors.initials: CS
authors.lastname: De Paiva
authors.forename: J K
authors.initials: JK
authors.lastname: Raince
authors.forename: A J
authors.initials: AJ
authors.lastname: McClellan
authors.forename: K P
authors.initials: KP
authors.lastname: Shanmugam
authors.forename: S B
authors.initials: SB
authors.lastname: Pangelinan
authors.forename: E A
authors.initials: EA
authors.lastname: Volpe
authors.forename: R M
authors.initials: RM
authors.lastname: Corrales
authors.forename: W J
authors.initials: WJ
authors.lastname: Farley
authors.forename: D B
authors.initials: DB
authors.lastname: Corry
authors.forename: D-Q
authors.initials: DQ
authors.lastname: Li
authors.forename: S C
authors.initials: SC
authors.lastname: Pflugfelder
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003228:Conjunctiva / Q000187:drug effects / Q000276:immunology*; D016572:Cyclosporine / Q000494:pharmacology; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D057134:Antibodies, Neutralizing; D018680:Cholinergic Antagonists; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D016572:Cyclosporine; D012601:Scopolamine