Golden Thea N, Garifallou James P, Conine Colin C, Simmons Rebecca A
Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania.
Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania.
bioRxiv. 2024 Sep 23:2024.09.19.613902. doi: 10.1101/2024.09.19.613902.
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 is established during neonatal development and 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 the resident immune system is established during neonatal development in the pancreas and spleen. We identified 9 distinct immune populations in the pancreatic islets and 8 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 CD8+ T cells in the islets and non-endocrine pancreas and in the spleen. IUGR-induced alterations were influenced by the tissue environment and the sex of the offspring. 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.
已知胰腺中的免疫细胞参与器官发育。然而，胰腺中的常驻免疫系统尚未完全明确。免疫细胞在病理学中也发挥作用，并与诸如宫内生长受限（IUGR）诱导的糖尿病等疾病有关。我们假设常驻免疫系统在新生儿发育期间建立，并被IUGR破坏。使用单细胞RNA测序和流式细胞术，我们在大鼠的近期胎儿（胚胎第22天）、新生儿（出生后第1、7和14天）的胰岛、非内分泌胰腺和脾脏中鉴定出许多免疫细胞群。通过流式细胞术，我们观察到常驻免疫系统在胰腺和脾脏的新生儿发育期间建立。通过单细胞RNA测序，我们在胰岛中鉴定出9个不同的免疫群体，在脾脏中鉴定出8个不同的免疫群体。胰腺或脾脏中免疫细胞的相对比例没有性别特异性差异。最后，我们使用双侧子宫动脉结扎术测试IUGR是否破坏了新生儿免疫系统。我们发现胰岛、非内分泌胰腺和脾脏中CD11B+HIS48-和CD8+T细胞的百分比有显著变化。IUGR诱导的改变受组织环境和后代性别的影响。未来确定这些免疫细胞在胰腺发育中作用的研究可能会发现导致IUGR后糖尿病发生的破坏途径。
