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Immunology - Ophthalmology - Physiology


NK Cells Promote Th-17 Mediated Corneal Barrier Disruption in Dry Eye
Published: Tuesday, May 08, 2012
Author: Xiaobo Zhang et al.

by 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

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+?d+ (~9.6%), CD3+NK+ (2%), CD3-NK+ (~4.4%), CD3+CD8a (~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.

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