Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by substantial heterogeneity in disease course, immune activity, and response to therapy. While genetic susceptibility contributes to MS risk, environmental and lifestyle factors are increasingly recognized as important modifiers of disease onset, progression, and treatment outcomes. Factors such as obesity, smoking, infections, diet, and metabolic dysfunction can shape immune responses by altering innate and adaptive immune signaling, ultimately translating into distinct clinical effects among patients. Understanding how environmental and lifestyle exposures shape immune programming is therefore essential for explaining variability in disease risk, clinical heterogeneity, and the mechanisms that drive disease activity in MS.

The goal of this Research Topic is to advance our understanding of how environmental and lifestyle factors shape immune responses in MS. Increasing evidence suggests that environmental exposures influence immune function through mechanisms such as metabolic reprogramming, mitochondrial stress, innate immune sensing, and alterations in tissue-immune interactions. These processes may ultimately affect disease susceptibility, progression, and response to disease-modifying therapies.

Recent technological advances (including multi-omics profiling, high-dimensional immune phenotyping, and improved experimental models) are enabling investigation into how environmental signals interact with immune pathways in MS. This Research Topic will bring together mechanistic, translational, and clinical studies exploring how environmental and lifestyle exposures influence immune regulation in MS. By integrating findings across human cohorts, experimental models, and emerging multi-omic approaches, this collection aims to uncover the biological mechanisms through which environmental factors shape MS risk and disease activity.

This Research Topic welcomes contributions that examine how environmental exposures and lifestyle factors shape immune responses in MS. We encourage submissions spanning basic, translational, and clinical research, including mechanistic studies, biomarker discovery, and studies linking environmental exposures to immune and clinical outcomes.

• Metabolic dysfunction and obesity as modifiers of immune responses in MS
• Environmental exposures such as recreational drug use, infections, and diet
• Sex- and age-dependent effects of environmental factors on immune signaling
• Innate immune sensing pathways, including mitochondrial stress and DAMP signaling
• Cytokine networks influenced by environmental factors
• Environmental modifiers of disease progression
• Multi-omics and systems biology approaches to gene/environment interactions in MS
• Experimental models investigating environmental drivers of neuroinflammation

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Environmental and Lifestyle Modifiers of Immune Responses in Multiple Sclerosis