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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355365/ https://www.ncbi.nlm.nih.gov/pubmed/35930633 http://dx.doi.org/10.1126/sciadv.abn9181 |
Sumario: | 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. |
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