title: T Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Contributes to Dry Eye Disease Pathogenesis by Promoting CD11b+ Myeloid Cell Maturation and Migration.
abstract: Growing evidence suggests that granulocyte-macrophage colony-stimulating factor (GM-CSF) contributes to T helper 17 (Th17) cell-associated immunoinflammatory diseases. The purpose of this study was to evaluate the effect of T cell-derived GM-CSF on CD11b+ myeloid cell function in dry eye disease (DED).
  
  
  
  In a murine model of DED, quantitative real-time PCR and ELISA were used to measure GM-CSF expression at the ocular surface, and flow cytometry was used to enumerate GM-CSF producing Th17 cells. A granulocyte-macrophage colony-stimulating factor neutralizing antibody was used topically in vivo and in an in vitro culture system to evaluate the role of GM-CSF in recruiting and maturing CD11b+ cells. Clinical disease severity was evaluated after topical administration of GM-CSF neutralizing antibody.
  
  
  
  In dry eye disease, GM-CSF is significantly upregulated at the ocular surface and the frequency of GM-CSF producing Th17 cells is significantly increased in the draining lymph nodes. In vitro neutralization of GM-CSF from CD4+ T cells derived from DED mice suppresses major histocompatibility complex II expression by CD11b+ cells and CD11b+ cell migration. Topical neutralization of GM-CSF in a murine model of DED suppresses CD11b+ maturation and migration, as well as Th17 cell induction, yielding a reduction in clinical signs of disease.
  
  
  
  T helper 17 cell-derived GM-CSF contributes to DED pathogenesis by promoting CD11b+ cell activation and migration to the ocular surface.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Dohlman
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Ding
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Reza
authors.initials: R
authors.lastname: Dana
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003228:Conjunctiva / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D058504:Th17 Cells / Q000473:pathology
chemical_list: D039481:CD11b Antigen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor