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A.K. Mircheff, Y. Wang, T. Nakamura, C. Ding, J.E. Schechter; Enhanced Lacrimal Gland Mucosal Immune Function Associated With Pregnancy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1944.
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The lacrimal gland is an important effector site of the mucosal immune system. Its stroma is populated by dimeric IgA– (dIgA–) secreting plasmacytes. Its parenchymal epithelium is specialized to express polymeric IgA receptors (pIgR), which mediate transcytotic secretion of dIgA, and also to generate a paracrine signaling milieu that supports differentiation and survivial of IgA+ plasmacytes. In contrast to the small intestine, where the site of dIgA synthesis is immediately subjacent to the mucosal immune barrier, the lacrimal gland is anatomically displaced from the corneal– and conjunctival epithelia. Previous studies in the Schechter laboratory have demonstrated that pregnancy is associated with decreased lacrimal gland fluid protein concentration and increased signs of ocular surface pathology, but also with increased expression of immunomodulatory cytokines and pronounced redistribution of infiltrating lymphocytes from periductal foci to interacinar spaces in the lacrimal gland,. The goal of the present study was to further explore the changes in rabbit lacrimal gland immunophysiology associated with pregnancy.
Term (29 day) pregnant– and age–matched, non–pregnant female rabbits were compared. Lacrimal gland fluid (LGF) was collected by cannulation of the main lacrimal excretory duct. Lacrimal glands lysates and LGF were resolved by SDS–PAGE, then analyzed by Western blot with appropriate primary and secondary antibodies.
Both membrane–bound– (∼62kD) and secreted– (∼59kD) isoforms of IgA were detected in lacrimal gland lysates and lacrimal gland fluid. Pregnancy significantly enhanced the amounts of both IgA isoforms in lacrimal gland lysates, but the increase for the secreted isoform was relatively greater. Pregnancy also significantly increased the abundances of pIgR and secretory component in lacrimal gland lysates. In contrast, it diminished the amount of IgG in lacrimal gland lysates.
The lacrimal gland undergoes immunophysiological changes during pregnancy that appear to mimic the changes the mammary gland undergoes during lactation. Since the local signaling milieus that support these mucosal immune functions also tend to support the generation of anti–inflammatory regulatory T cells, we propose that the increased ocular surface pathology during pregnancy reflects a divergence of immunophysiological processes in the lacrimal gland from processes in the cornea and conjunctiva.
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