NK cells promote Th-17 mediated corneal barrier disruption in dry eye

PLoS One. 2012;7(5):e36822. doi: 10.1371/journal.pone.0036822. Epub 2012 May 8.


Background: The conjunctiva contains a specialized population of lymphocytes that reside in the epithelium, named intraepithelial lymphocytes (IEL).

Methodology/principal findings: 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/significance: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Chemokine CCL20 / genetics
  • Chemokine CCL20 / immunology
  • Conjunctiva / immunology
  • Conjunctiva / pathology
  • Cornea / immunology*
  • Cornea / pathology
  • Dry Eye Syndromes / genetics
  • Dry Eye Syndromes / immunology*
  • Dry Eye Syndromes / pathology
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / immunology
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Th17 Cells / immunology*
  • Th17 Cells / pathology


  • Antigens, CD
  • CCL20 protein, mouse
  • Chemokine CCL20
  • Il17a protein, mouse
  • Interleukin-17
  • Matrix Metalloproteinase 3
  • Mmp3 protein, mouse