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D. R. Saban, S. K. Chauhan, R. Dana; Identification and Function of Novel Langerin Positive Dendritic Cells in the Cornea. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1545.
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The recent discovery of langerin positive (CD207+) dermal DCs (dDC) in the skin was a key breakthrough, as it disproved the longstanding tenet that local immunity is mediated chiefly by Langerhans cells (LC). The normal cornea is also endowed with resident DCs, and some of which are distinct from epithelial LCs. We therefore explored herein whether a population akin to dDCs exists in the normal cornea, and examined their potential flux to regional lymph nodes (LN) following corneal allo-transplantation.
Normal C57BL/6 mouse corneas (n=30) were collected and their epithelium carefully separated from the stroma following EDTA (20mM) incubation. Corneal stromas were pooled separately, as were epithelia, and digested enzymatically for FACS analysis of CD45; CD11c; CD207 (dDC and LC marker); CD205 (dDC and LC marker); and CD103 (dDC marker). Immunohistochemistry of corneal flat mounts was also examined by confocal microscopy to verify FACS results. Furthermore, BALB/c mice were allografted with C57BL/6 corneas and regional LN were subsequently examined 5 days post-transplantation by FACS analysis (for CD11c, CD207, CD8a, and CD103) to enumerate migrated dDCs vs. LCs.
Nearly all DCs (CD45+ CD11c+) in the corneal epithelium were CD207+; and strikingly, most (76%) stromal DCs were also CD207+ (albeit slightly lower in MFI). Both subsets were CD205+ as well, but the stromal subset again had a slightly lower MFI. However, only the stromal subset expressed CD103+ and this was verified immunohistochemicaly (along with CD207+). Interestingly, frequencies of this stromal DC subset (i.e., CD11c+ CD8a- CD207+ CD103+) decreased dramatically (by 4-fold) in ipsilateral LNs following transplantation relative to naïve mice; whereas those of the epithelial DC subset (CD11c+ CD8a- CD207+ CD103-) markedly increased. A similar, but much less dramatic, trend was seen in the contralateral LN of transplanted mice as well.
Our findings indicate that a population akin to dermal DCs exists in corneal stroma during the steady-state. This population is CD11c+ CD8a- CD207+ CD103+; whereas the epithelial LC population is CD11c+ CD8a- CD207+ CD103-. Interestingly, the significant and diametrically opposed flux of such stromal DCs vs. LCs to LNs following transplantation, suggests that these subsets may have differing functions in alloimmunity.
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