Phosphatase PP2A is essential for T <subscript>H</subscript> 17 differentiation.

Phosphatase PP2A expression levels are positively correlated to the clinical severity of systemic lupus erythematosus (SLE) and IL17A cytokine overproduction, indicating a potential role of PP2A in controlling T H 17 differentiation and inflammation. By generating a mouse strain with ablation of the catalytic subunit α of PP2A in peripheral mature T cells (PP2A cKO), we demonstrate that the PP2A complex is essential for T H 17 differentiation. These PP2A cKO mice had reduced T H 17 cell numbers and less severe disease in an experimental autoimmune encephalomyelitis (EAE) model. PP2A deficiency also ablated C-terminal phosphorylation of SMAD2 but increased C-terminal phosphorylation of SMAD3. By regulating the activity of RORγt via binding, the changes in the phosphorylation status of these R-SMADs reduced Il17a gene transcription. Finally, PP2A inhibitors showed similar effects on T H 17 cells as were observed in PP2A cKO mice, i.e., decreased T H 17 differentiation and relative protection of mice from EAE. Taken together, these data demonstrate that phosphatase PP2A is essential for T H 17 differentiation and that inhibition of PP2A could be a possible therapeutic approach to controlling T H 17-driven autoimmune diseases.

Competing Interests: The authors declare no conflict of interest.