Tspan2 is involved in anti-infectious immune responses and CNS autoimmunity

Abstract

Abstract Tetraspanin proteins regulate critical cellular processes in CNS development and immune defence against pathogens. Through lateral association within membrane domains or binding of interaction partners these proteins are involved in pathogen recognition, proliferation and trafficking of immune cells, as well as cell differentiation and motility in the CNS. The tetraspanin family member Tspan2 was originally identified in oligodendrocyte lineage cells. It has been implicated in immunoregulation in the CNS as Tspan2−/− mice show increased microglia and astrocyte activation in the absence of inflammatory stimuli. A role of Tspan2 in CNS inflammation and anti-infectious immune responses remains to be elucidated. In newly generated Tspan2/DTR/EGFP reporter mice, we detected Tspan2 expression predominantly in mature oligodendrocytes in the CNS and an enhanced clinical severity of experimental autoimmune encephalomyelitis upon immunization with MOG35–55 peptide in Tspan2−/− mice. In peripheral lymphoid organs, Tspan2 expression was found in neutrophils and the majority of dendritic cells (DCs). Tspan2−/− DCs showed reduced uptake of zymosan as compared to wild-type (WT) DCs indicating that Tspan2 affects fungal recognition by DCs. In the absence of Tspan2 neutrophils exhibited a reduced accumulation of reactive oxygen species (ROS) and enhanced migration to inflammatory sites in thioglycollate-induced peritonitis as compared to WT neutrophils. LPS challenge in vivo induced increased production of the proinflammatory cytokines TNF, IL-1β, and IL-6 in the spleens of Tspan2−/− as compared to WT mice. These data provide first evidence that Tspan2 regulates anti-infectious immune responses as well as CNS autoimmunity.