title: NK cells promote Th-17 mediated corneal barrier disruption in dry eye.
abstract: BACKGROUND
  The conjunctiva contains a specialized population of lymphocytes that reside in the epithelium, named intraepithelial lymphocytes (IEL).
  
  
  RESULTS
  Here we characterized the IEL population prior to and after experimental desiccating stress (DS) for 5 or 10 days (DS5, DS10) and evaluated the effect of NK depletion on DS. The frequency of IELs in normal murine conjunctiva was CD3(+)CD103(+) (~22%), CD3(+)γδ(+) (~9.6%), CD3(+)NK(+) (2%), CD3(-)NK(+) (~4.4%), CD3(+)CD8α (~0.9%), and CD4 (~0.6%). Systemic depletion of NK cells prior and during DS led to a decrease in the frequency of total and activated DCs, a decrease in T helper-17(+) cells in the cervical lymph nodes and generation of less pathogenic CD4(+)T cells. B6.nude recipient mice of adoptively transferred CD4(+)T cells isolated from NK-depleted DS5 donor mice showed significantly less corneal barrier disruption, lower levels of IL-17A, CCL20 and MMP-3 in the cornea epithelia compared to recipients of control CD4(+)T cells.
  
  
  CONCLUSIONS
  Taken together, these results show that the NK IELs are involved in the acute immune response to desiccation-induced dry eye by activating DC, which in turn coordinate generation of the pathogenic Th-17 response.
authors.affiliation: Department of Ophthalmology, Ocular Surface Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhang
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Volpe
authors.forename: Niral B
authors.initials: NB
authors.lastname: Gandhi
authors.forename: Chris S
authors.initials: CS
authors.lastname: Schaumburg
authors.forename: Karyn F
authors.initials: KF
authors.lastname: Siemasko
authors.forename: Solherny B
authors.initials: SB
authors.lastname: Pangelinan
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kelly
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Hayday
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Li
authors.forename: Michael E
authors.initials: ME
authors.lastname: Stern
authors.forename: Jerry Y
authors.initials: JY
authors.lastname: Niederkorn
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
authors.forename: Cintia S
authors.initials: CS
authors.lastname: De Paiva
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology; D003228:Conjunctiva / Q000276:immunology / Q000473:pathology; D003315:Cornea / Q000276:immunology* / Q000473:pathology; D015352:Dry Eye Syndromes / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D015703:Antigens, CD; C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; C098680:Il17a protein, mouse; D020381:Interleukin-17; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse