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Austin K. Mircheff, Yanru Wang, Billy X. Pan, Leili Parsa, Padmaja B. Thomas, Melvin D. Trousdale, Joel E. Schechter, Chuanqing Ding; Reproductive Hormones Profoundly Influence the Dynamics of Immunohomeostasis in the Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3749.
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© ARVO (1962-2015); The Authors (2016-present)
Lacrimal gland (LG) immunohomeostasis is not a single state but a dynamic process of tightly orchestrated paracrine mediator expression. One of the mediators, prolactin, also is a hormone that becomes elevated during pregnancy. Abundance of prolactin mRNA in LG changes dramatically but seemingly erratically late in pregnancy: it may increase in one LG and decrease in the other. Small periductal/perivenular immune cell accumulations containing prolactin are more frequent in high prolactin (high PRL) LG.
LG from 6 non-pregnant (np) and 6 term-pregnant (tp) rabbits were analyzed by confocal immunofluorescence. Transcript abundances were determined in whole LG extracts and laser capture microdissected samples
Abundances of CCL2, IL-2, IL-6, IL-10, and BAFF mRNAs correlated strongly with prolactin mRNA in LG extracts. IL-6, IL-10, and BAFF mRNAs were detected only in immune cell accumulations in npLG but also in acinar and ductal cells of tpLG; abundances were higher in high PRL tpLG. CCL2 mRNA was present in acinar cells and immune cell accumulations of npLG; in high PRL tpLG it also was present in ductal cells. Prolactin mRNA was present in acinar cells, ductal cells, and immune cell accumulations of npLG. Its abundance was lower in acinar cells of both high PRL and low PRL tpLG. It was lower in ductal cells of low PRL tpLG and higher in ductal cells of high PRL tpLG. Prolactin immunopositivity was concentrated in ductal cells but also present in acinar cells and immune cell accumulations. IL-10+ cells were scattered through the interacinar stroma and rarely present in accumulations.
We propose that CCL2 recruits immune cells; IL-2, IL-6, BAFF, and prolactin support their survival; and IL-10 suppresses their expression of other TH1 cytokines. The hormonal milieu of pregnancy decreases expression of prolactin in acinar and ductal cells but increases expression of CCL2, IL-6, IL-10, and BAFF. Increased levels of the paracrine mediators recruit more immune cells to accumulations and also up-regulate their expression of BAFF. Paracrine mediators released from the accumulations then signal back to ductal cells; above certain threshold levels, the mediators over-ride the systemic signals that suppressed prolactin expression. Increased duct cell prolactin then drives expansion of the accumulations. This positive feed-back may sometimes cause the accumulations to become pathological.
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