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

Xiaobo Zhang, Eugene A. Volpe, Niral B. Gandhi, Chris S. Schaumburg, Karyn F. Siemasko, Solherny B. Pangelinan, Scott D. Kelly, Adrian C. Hayday, De Quan Li, Michael E. Stern, Jerry Y. Niederkorn, Stephen C. Pflugfelder, Cintia S. de Paiva

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere36822
JournalPloS one
Volume7
Issue number5
DOIs
StatePublished - May 8 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Zhang, X., Volpe, E. A., Gandhi, N. B., Schaumburg, C. S., Siemasko, K. F., Pangelinan, S. B., Kelly, S. D., Hayday, A. C., Li, D. Q., Stern, M. E., Niederkorn, J. Y., Pflugfelder, S. C., & de Paiva, C. S. (2012). NK cells promote Th-17 mediated corneal barrier disruption in dry eye. PloS one, 7(5), [e36822]. https://doi.org/10.1371/journal.pone.0036822