Effects of environmental enrichment on lymph node mitochondrial-redox status and immune response in adult male C57BL/6 mice.

Environmental enrichment (EE) is a well-established experimental paradigm characterized by enhanced social interaction, cognitive stimulation, and voluntary physical activity, designed to model biologically relevant ecological complexity. In the field of neuroscience, EE has been demonstrated to enhance learning, memory, and attention, while also providing resilience against stress-related neuropsychiatric disorders and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. Beyond the central nervous system (CNS), EE has emerged as a systemic modulator of immune function. Experimental evidence indicates that EE influences cytokine production, immune cell activation, and stress-induced immune dysregulation, supporting its role in maintaining immune homeostasis. However, despite these advances, the impact of EE on lymph nodes, the primary anatomical sites of adaptive immune activation, remains poorly characterized. Lymph nodes provide the metabolic and redox framework required for antigen presentation, T- and B-cell activation, clonal expansion, and effector differentiation. These processes are energetically demanding and highly sensitive to redox balance, which regulates mitochondrial metabolism, intracellular signaling thresholds, and cytokine production. Disruption of redox homeostasis within lymphoid tissues promotes oxidative stress, exaggerated Th1 polarization, and excessive interferon-gamma (IFN-γ) production, features commonly associated with aging, autoimmune disease, and chronic inflammatory states.