lncRNA-GM targets Foxo1 to promote T cell-mediated autoimmunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35930633.
- Also identified by DOI 10.1126/sciadv.abn9181 and PMC identifier 9355365.
- Licence recorded as CC BY-NC.
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Abstract
RNA-RBP interaction is important in immune regulation and implicated in various immune disorders. The differentiation of proinflammatory T cell subset T<sub>H</sub>17 and its balance with regulatory T cell (T<sub>reg</sub>) generation is closely related to autoimmune pathogenesis. The roles of RNA-RBP interaction in regulation of T<sub>H</sub>17/T<sub>reg</sub> differentiation and autoinflammation remain in need of further investigation. Here we report that lncRNA-GM polarizes T<sub>H</sub>17 differentiation but inhibits iT<sub>reg</sub> differentiation by reducing activity of Foxo1, a transcriptional factor that is important in inhibiting T<sub>H</sub>17 differentiation but promoting T<sub>reg</sub> generation. <i>lncRNA-GM</i>-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 <i>Il23r</i> transcription. The human homolog of lncRNA-GM (AK026392.1) also polarizes human T<sub>H</sub>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.