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Aire+ Cell Depletioin Results in Expansion of Activated T Cells in Pregnant Mice

ABSTRACT: We explored the role of the autoimmune regulator (Aire) gene in supporting fetal tolerance during pregnancy with transgenic diphtheria toxin receptor (Aire-DTR) mice, in which Aire-expressing populations can be deleted by injection of diptheria toxins (DT). Aire-expressing cell depletion was found to cause intruterine growth restriction (IUGR) in both allogenic and syngeneic pregnancies. This phenotype is immune-mediated, as IUGR is rescued in Rag1-deficient mice, and involves a memory response, as demonstrated by severe IUGR in second pregnancies. We further explored this phenotype through single-cell RNA sequencing of leukocytes obtained from the secondary lymphoid organs (uterine and non-uterine-draining lymph nodes) of wild-type (WT) and Aire-DTR pregnant dams during allogeneic pregnancy. Transciptomic data reveals a shift in population distributions from naïve to effector CD4+ and CD8+ T cells in Aire-DTR mice. Within the effector CD4+ compartment, there was a significant shift away from Tregs and toward mature T effectors, most notably T follicular helper (Tfh) and Th17 cells. These findings support the idea that Aire is essential in maintaining immune homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE174521 | GEO | 2021/05/18

REPOSITORIES: GEO

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