lncRNA-GM targets Foxo1 to promote T cell-mediated autoimmunity.

RNA-RBP interaction is important in immune regulation and implicated in various immune disorders. The differentiation of proinflammatory T cell subset T H 17 and its balance with regulatory T cell (T reg ) generation is closely related to autoimmune pathogenesis. The roles of RNA-RBP interaction in regulation of T H 17/T reg differentiation and autoinflammation remain in need of further investigation. Here we report that lncRNA-GM polarizes T H 17 differentiation but inhibits iT reg differentiation by reducing activity of Foxo1, a transcriptional factor that is important in inhibiting T H 17 differentiation but promoting T reg generation. lncRNA-GM -deficient mice were protected from experimental autoimmune encephalomyelitis. Mechanistically, lncRNA-GM directly binds to cytoplasmic Foxo1, thus inhibiting its activity through blocking dephosphorylation of Foxo1 by phosphatase PP2A to promote Il23r transcription. The human homolog of lncRNA-GM (AK026392.1) also polarizes human T H 17 differentiation. Our study provides mechanistic insight into the interaction of lncRNA and transcriptional factor in determining T cell subset differentiation during T cell-mediated autoimmune diseases.