Abstract
Purpose:
Plasmacytoid dendritic cells (pDC) represent a highly functional subset of bone marrow (BM)-derived cells and play a key role in linking the innate and adaptive immune responses, but little is known about the nature and the role of pDCs in the cornea. The aim of this study is to investigate the role of corneal pDC in the immune responses in corneal inflammation
Methods:
Corneal inflammation was induced by placement of 3 intrastromal 10-0 nylon sutures. Corneal pDCs were depleted by subconjunctival (s.c.) injection of diphtheria toxin (DT) or by PBS (sham controls) into BDCA-2-DTR mice. Cornea opacity was scored in a 0-5 scale. Corneas and draining lymph nodes (dLNs) were excised and single cell suspensions obtained for flow cytometry assay by staining with antibodies to CD45 (BM-derived cells), Gr-1 (neutrophils), NK 1.1 (NK cells), F4/80 (macrophages), CD11c (dendritic cells), CD3, CD4, CD8 (T cells), and CD19 (B cells)
Results:
We observed a significant and surprising increase in the opacity in pDC-depleted corneas at day 7 (3.5) and 14 (3.5) vs. (0.8 and 0.6 respectively, P<0.001) as compared to sham controls. Similarly, a significantly increased influx of CD45+ (3-fold) was noted in pDC-depleted corneas as compared to sham controls was seen. Also, there is an increased density of neutrophils (3.1-fold), macrophages (2.8-fold) and dendritic cells (3-fold) as compared to sham controls; while T cells, NK cells and B cells didn’t show significant changes. Depletion of corneal pDC did not have an effect on CD4+ T cells and NK cells in dLNs on days 7 and 14. However, there was a modest increase in total T cells, CD8+ T cells (1.35-fold), as well as B cells (1.3-fold)
Conclusions:
This data demonstrate that corneal pDC may mediate innate and adaptive immune responses in the cornea. Depletion of pDC results in increased influx and shift in balance of infiltrating cells in the cornea during inflammation. Furthermore, pDC may play a role in regulating the adaptive immune responses in dLN
Keywords: 557 inflammation •
555 immunomodulation/immunoregulation •
480 cornea: basic science