Spleen glia are a transcriptionally unique glial subtype interposed between immune cells and sympathetic axons.

Glia are known to play important roles in the brain, the gut, and around the sciatic nerve. While the gut has its own specialized nervous system, other viscera are innervated solely by autonomic nerves. The functions of glia that accompany autonomic innervation are not well known, even though they are one of the most abundant cell types in the peripheral nervous system. Here, we focused on non-myelinating Schwann cells in the spleen, spleen glia. The spleen is a major immune organ innervated by the sympathetic nervous system, which modulates immune function. This interaction is known as neuroimmune communication. We establish that spleen glia can be visualized using both immunohistochemistry for S100B and GFAP and with a reporter mouse. Spleen glia ensheath sympathetic axons and are localized to the lymphocyte-rich white pulp areas of the spleen. We sequenced the spleen glia transcriptome and identified genes that are likely involved in axonal ensheathment and communication with both nerves and immune cells. Spleen glia express receptors for neurotransmitters made by sympathetic axons (adrenergic, purinergic, and Neuropeptide Y), and also cytokines, chemokines, and their receptors that may communicate with immune cells in the spleen. We also established similarities and differences between spleen glia and other glial types. While all glia share many genes in common, spleen glia differentially express genes associated with immune responses, including genes involved in cytokine-cytokine receptor interactions, phagocytosis, and the complement cascade. Thus, spleen glia are a unique glial type, physically and transcriptionally poised to participate in neuroimmune communication in the spleen.