The Effect of Intrauterine Growth Restriction on the Developing Pancreatic Immune System

Immune cells in the pancreas are known to participate in organ development. However, the resident pancreatic immune system has yet to be fully defined. Immune cells also play a role in pathology and are implicated in diseases such as diabetes induced by intrauterine growth restriction (IUGR). We hypothesized that the resident immune system continues to develop during the neonatal period and is disrupted by IUGR. Using single-cell RNAseq and flow cytometry we identified many immune cell populations in the near-term fetus (at embryologic day 22) and neonatal (postnatal day 1, 7, &14) islets, non-endocrine pancreas, and the spleen in the rat. Using flow cytometry, we observed that the resident immune system dynamically changes during neonatal development in the pancreas and spleen. We identified 14 distinct immune populations in the pancreatic islets and 13 distinct immune populations in the spleen by single-cell RNAseq. There were no sex-specific differences in the relative proportion of immune cells in the pancreas or spleen. Finally, we tested if IUGR disrupted the neonatal immune system using bilateral uterine artery ligation. We found significant changes to the percentage of CD11B+ HIS48- and B cells in the islets and non-endocrine pancreas. IUGR-induced alterations were influenced by the tissue environment. Future research to define the role of these immune cells in pancreatic development may identify disrupted pathways that contribute to the development of diabetes following IUGR.