Enriched environment regulates thymocyte development and alleviates experimental autoimmune encephalomyelitis in mice

Abstract

Environmental and social factors have profound impacts on immune homeostasis. Our work on environmental enrichment (EE) has revealed a novel anti-obesity and anticancer phenotype associated with enhanced activity of CD8+ cytotoxic T lymphocytes in secondary lymphoid tissues. Here we investigated how an EE modulated thymus and thymocyte development. EE decreased thymus mass and cellularity, decreased the double positive thymocyte population, increased the proportion of CD8+ T cells, reduced the CD4:CD8 ratio, and downregulated CD69 expression in T cells. In a model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE), EE alleviated symptoms, inhibited spinal cord inflammation through regulation of type 1 T-helper cells mediated by glucocorticoid receptor signaling, and prevented EAE-induced thymic disturbance. Our mechanistic studies demonstrated that hypothalamic BDNF activated a hypothalamic-pituitary-adrenal axis mediating the EE’s thymic effects. Our results indicate that a lifestyle intervention links the nervous, endocrine, and adaptive immune system, allowing the body to adapt to internal and external environments.

CSF1R inhibitor PLX5622 and environmental enrichment additively improve metabolic outcomes in middle-aged female mice

“…A major candidate for this stimulus is BDNF, the central coordinator for many CNS and peripheral effects of EE. We previously demonstrated that neuronal overexpression of BDNF reproduces various effects of EE including systemic metabolism, adipose remodeling, immune modulations, cancer, and aging [9][10][11][40][41][42].…”

Enriched environment inhibits breast cancer progression in obese models with intact leptin signaling

“…We have used a mouse model of environmental enrichment (EE) to study an active lifestyle influence on health and diseases (Cao et al 2004, Cao & During 2012, During et al 2015, Foglesong et al 2016, Xiao et al 2016, 2019, Mcmurphy et al 2018. EE refers to a housing with increased space, physical activity and social interactions that facilitate enhanced sensory, cognitive, motor and social stimulation (Nithianantharajah & Hannan 2006).…”

Environmental enrichment improves cognitive symptoms and pathological features in a focal model of cortical damage of multiple sclerosis

“…One study demonstrated that EE improved chemotaxis of phagocytes and lymphocytes and reduces the oxidative stress in immune cells, which strengthened the responses to infection (Arranz et al, 2010). Ultimately, it was demonstrated that EE, in EAE model, modulates thymus and thymocyte development inducing an enhanced activity of CD8+ cytotoxic T lymphocytes in secondary lymphoid tissues (Xiao et al, 2019). This work provides additional evidence that EE could exert immunomodulatory effects.…”

“…Additionally, EE improves remyelination by promoting adult neural progenitor mobilization in the EAE model (Fields, 2008;Magalon et al, 2007). Furthermore, EE enhances CD8+ cytotoxic T lymphocytes activity in secondary lymphoid tissues in EAE (Xiao et al, 2019).…”