[en] BACKGROUND AND AIMS: CD71+ erythroid cells are enriched during pregnancy with immuno suppressive properties. We investigated the frequency and functionality of CD71+ erythroid cells in peripheral blood, cord blood, and placenta of inflammatory bowel disease [IBD] patients versus healthy controls [HCs]. We aimed to determine their role in IBD pathogenesis during pregnancy. METHODS: Peripheral blood was collected at preconception, the first, second and third 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 quantitative polymerase chain reaction [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 with HCs. Placenta and cord blood CD71+ erythroid cells from IBD patients exhibited impaired functionality and expressed lower inhibitory molecules including VISTA, TGF-β, and reactive oxygen species [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 allogeneic pregnancy model resulted in upregulation of TLRs, IL-6, and CXCL-1, and enhanced production of TNF-α, in intestinal tissues. In contrast, TGF-β gene expression was reduced. Excessive inflammatory response in the gut [e.g. TNF-α] affects intestinal integrity and CD71+ erythroid cells impact on the 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 gastrointestinal tract, characterised by lower Tregs, higher IL-6, and TNF-α, and dysbiosis.
Disciplines :
Immunology & infectious disease
Author, co-author :
Dunsmore, Garett ✱; Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > Physiologie générale et des systèmes ; Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. ; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Koleva, Petya ✱; Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Ghobakhloo, Nafiseh; Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. ; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Sutton, Reed; Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
Ambrosio, Lindsy; Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
Meng, Xuanyi; Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Hotte, Naomi; Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
Nguyen, Vivian; Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
Madsen, Karen L; Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
Dieleman, Levinus A; Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.
Huang, Vivian; Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada. ; Division of Gastroenterology, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada.
Elahi, Shokrollah; Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. ; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
✱ These authors have contributed equally to this work.
Language :
English
Title :
Lower Abundance and Impaired Function of CD71+ Erythroid Cells in Inflammatory Bowel Disease Patients During Pregnancy.
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