Harnessing Monocyte Dynamics for Treatment of Multiple Sclerosis (MS); Insights from Experimental Model Studies

Monocytes are central to the innate immune system’s response to infection or injury. In murine, these cells are classified into distinct subsets: classical monocytes, defined by elevated Ly6C expression (Ly6C^hi), intermediate monocytes (Ly6C^int), and non-classical inflammatory monocytes, characterized by low Ly6C expression (Ly6C^low). Monocytes recruited to tissues differentiate into macrophages, which can be pro-inflammatory or anti-inflammatory, thereby influencing disease processes and outcomes. The principal function of classical monocytes is the mediation of pro-inflammatory reactions, whereas non-classical monocytes are associated with repair and anti-inflammatory processes, patrolling the lumen of the vessels. Growing evidence highlights the importance of monocytes in Multiple Sclerosis (MS), an autoimmune and neurodegenerative disease of the central nervous system (CNS). Recent studies indicate that modulation of the innate immune system, focusing specifically on the shift from Ly6C^hi to Ly6C^low monocytes, is an effective therapeutic strategy for neurodegenerative diseases, such as Alzheimer’s and MS. This transition is crucial for switching the immune response from inflammation to tissue repair and inflammation resolution, emphasizing the plasticity of monocytes and their potential as targets in MS. This review differs from prior studies in that it focuses solely on animal models of MS, which either directly perturb or study monocytes, or where therapeutic approaches mediate their protective effects through monocytes. Such details permit a subtle comprehension of monocyte dynamics in the context of MS.