Lower Abundance and Impaired Function of CD71+ Erythroid Cells in Inflammatory Bowel Disease Patients During Pregnancy.
J Crohns Colitis. 2018 Oct 01;:
Authors: Dunsmore G, Koleva P, Ghobakhloo N, Sutton RT, Ambrosio L, Meng X, Hotte N, Nguyen V, Madsen KL, Dieleman LA, Huang V, Elahi S
Background and Aims: CD71 + erythroid cells are enriched during pregnancy with immunosuppressive properties. We investigated the frequency and functionality of CD71 + erythroid cells in peripheral blood, cord blood and placenta of IBD patients vs. healthy controls. We aimed to determine their role in IBD pathogenesis during pregnancy.
Methods: Peripheral blood was collected at preconception, 1st, 2nd, 3rd trimesters and postpartum. Cord blood and placental tissues were collected at the time of birth. Cells from different specimens were subjected to immune-phenotyping and functional assays. CD71+ erythroid cells were purified for qPCR analysis. Using an allogeneic mouse model of pregnancy, the effects of CD71+ erythroid cells depletion on intestinal homeostasis and dysbiosis was studied.
Results: IBD patients had lower CD71+ erythroid cells during pregnancy compared to HCs. Placenta and cord blood CD71+ erythroid cells from IBD patients exhibited impaired functionality and expressed lower inhibitory molecules including VISTA, TGF- and ROS. Lower CD71+ erythroid cells were correlated with reduced regulatory T cells and increased immune-activation in IBD patients. Depletion of CD71+ erythroid cells in an allogenic pregnancy model resulted in upregulation of TLRs, IL-6, CXCL-1 and enhanced production of TNF- in intestinal tissues. In contrast, TGF- gene expression was reduced. Excessive inflammatory response in the gut (e.g. TNF-) impacts intestinal integrity and CD71+ erythroid cells impact gut’s bacterial composition.
Conclusions: Reduced frequency and/or impaired functionality of CD71+ erythroid cells during pregnancy may predispose IBD patients to a more pro-inflammatory milieu in their GI tract, characterized by lower Tregs, higher IL-6, TNF- and dysbiosis.
PMID: 30272151 [PubMed – as supplied by publisher]