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Austin K Mircheff, Yanru Wang, Dwight W Warren, Joel Schechter, Chuanqing Ding; Pregnancy can increase accumulation and activation of cells and functions associated with Sjögren’s ectopic lymphoid structures. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4478.
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© ARVO (1962-2015); The Authors (2016-present)
Having carried a pregnancy to term doubles risk that Sjögren’s disease (SjD) will manifest at menopause. mRNAs for numerous chemokines, cytokines, and functional proteins that participate in Sjögren’s ectopic lymphoid structures (ELS) can be detected in lacrimal glands that appear free of ELS. We therefore asked how pregnancy impacts expression of the SjD-implicated transcripts.
Six 29-day pregnant rabbits and six virgin rabbits had been housed in a barrier-free facility in the same meteorological setting. qRT-PCR determined abundances of 62 transcripts in each lacrimal gland. Pearson’s test identified clusters of positively- and negatively-correlating transcripts.
mRNAs for IGF-1B, CD1d, and CD138 increased significantly in the glands from pregnant rabbits, and mRNA for IL‑17A decreased, but the glands sorted to two subgroups with respect to other transcripts. mRNAs for E-selectin, VCAM-1, MHC I, CXCL12, CXCL13, LT-β, and CD59 were significantly higher in one subgroup, and cells that expressed CXCL13 and LT-β, both essential for germinal center formation, engaged in positive crosstalk with each other. Numerous transcripts, including mRNAs for CCL2, CCL4, IL-1, IL-2, IL-4, IL-6, IL-10, BAFF, CD4, CD8, CD25, CTLA-4, CD28, CD40L, CD40, CD86, MHC II, CD40L, CD72, and PRL, were significantly higher in the other subgroup; extensive strong, positive correlations suggested a complex network comprising epithelial cells, antigen presenting cells, multiple T cell lineages, and relatively immature B cells. The network developed to markedly different levels in different glands of the subgroup. Interestingly, it engaged in strong, negative crosstalk with cells that expressed mRNAs for E-selectin, IGF-1B, and MHC I; moreover, Pearson’s ρ values for its associations with cells that expressed CXCL13 and LT-β were consistently negative.
Pregnancy can interact with stochastic phenomena to increase accumulation or activation of many of the various cells types and functions which contribute to ELS, but intrinsic, counter-regulatory phenomena prevent them all from coalescing in any given gland. Thus, abrogation of the counter-regulatory phenomena later in life may be critical before the components can assemble into ELS.
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