Sympathetic innervation of human cervical lymph nodes: A potential neuroimmunomodulatory target for the treatment of T-cell-driven autoimmune diseases like MS?

Abstract

Multiple sclerosis (MS) is a progressive neurological autoimmune disease characterized by neuroinflammation and immune dysfunction. Existing treatments primarily focus on managing symptoms, highlighting the need for preventive and curative approaches. Recent research suggests that the sympathetic nervous system, particularly through beta-2-adrenergic receptor (β₂-AR) signaling on T cells, may play a role in regulating MS-related autoimmune responses, offering a potential novel therapeutic target. This study investigated the presence of sympathetic nerves and their proximity to T cells in human deep cervical lymph nodes (DCLN), which are implicated in MS autoimmune responses. Cadaveric dissections and microscopic imaging were employed to examine the presence of sympathetic nerves, their proximity to T cells and whether T cells express β₂-ARs. Sympathetic nerves were observed in 108 of 141 DCLNs and were located in varying regions of the lymphoid tissue, including active immune sites where they were in proximity to β₂-AR–expressing T cells. The observations of this study support the notion of a neuroimmune link in human DCLNs, which could represent a promising treatment target in T-cell-driven autoimmune diseases of the central nervous system, including MS.