Immune cell differentiation in response to neglect-related early life stress exposure 3749

Description Environmental exposures, including early life stress (ELS), accumulate from birth and impact biological development to influence health and disease. Childhood neglect is a significant source of ELS and can take many forms. After the COVID-19 pandemic, deeper understanding of how ELS exposure shapes the early immune system is of interest. We used a maternal separation with early weaning paradigm to study the effects of neglect-related ELS on immune cells of select lymphoid tissues in the defined early life period (postnatal day (PD) 0-21) in C57BL/6J mice. We hypothesized that ELS exposure would suppress early lymphocyte development and dampen basal cytokine production. To test this hypothesis, we used multiplex assays to profile secretory cytokines and single-cell RNA sequencing (scRNA-seq) to define the heterogeneity of cells isolated from the thymus and spleen at postnatal age PD21. Neglect-related stress conditions were simulated with scheduled dam-pup separation (physical neglect) and early weaning to high carbohydrate diet (malnutrition). Control pups were not separated and maintained on dam’s milk to the standard wean date. ELS elicited suppressive effects on Th2-related cytokines, such as IL-4 and IL-5, and stimulatory cytokine IL-15. Comparing control vs. ELS-derived scRNA-seq profiles revealed a subset of splenic stem cells were depleted in ELS mice. This study provides preliminary insight on ELS-mediated consequences on immune cell differentiation. Funding Sources NIH/NIA T32 AG020494; NIH/NIMHD 5U54MD006882-10; UNTHSC Dept. of Microbiology, Immunology, and Genetics Intramural Grant; UNTHSC Dept. of Physiology & Anatomy SEED Grant Topic Categories Hematopoiesis and Immune System Development (HEM)