Extrapituitary prolactin promotes generation of Eomes-positive helper T cells mediating neuroinflammation

Abstract

Significance We have previously demonstrated that induction of pathogenic eomesodermin-positive CD4 + T cells (Eomes + T helper [Th] cells) is associated with transition from an acute stage to a later stage of experimental autoimmune encephalomyelitis (EAE). In the late phase of EAE, B cells and non-B cell antigen-presenting cells (APCs) recruited to the central nervous system strikingly up-regulate prolactin (PRL). The PRL-producing APCs have the potential to promote generation of Eomes + Th cells from naïve T cells in an MHC class II-restricted manner, and therapies inhibitory for PRL production suppress the induction of Eomes + Th cells and ameliorate clinical signs of EAE. Our study highlights the unexpected role of extrapituitary PRL in the development of persistent neuroinflammation.