Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells

Abstract

T-helper 17 (Th17) cells are involved in the occurrence and development of several inflammation-associated diseases. Interleukin (IL)-17, the main cytokine secreted by differentiated Th17 cells, mediates immunoreactions and plays important roles in immunological diseases, including psoriasis, rheumatic arthritis, and inflammatory bowel disease. The maturation and stabilization of the differentiated Th17 cell phenotype are associated with the expression of IL-17A, which is induced by the activation of signal transducer and activator of transcription 3 (STAT3). Prohibitin 1 (PHB1) also plays an essential role in T-cell activation. However, the molecular mechanisms underlying Th17 cell differentiation and the role of PHB1 have not yet been completely elucidated, and this information would greatly facilitate the development of therapeutic strategies to prevent or treat immune-associated diseases. Here, we found that STAT3 expression was correlated with PHB1 mRNA expression during Th17 cell differentiation. Double-labeling immunofluorescence assay results showed that exogenous PHB1 and STAT3 proteins were not only located primarily in the nucleus but also in the cytoplasm of human Th17 cells. Co-immunoprecipitation assays of Th17 cells revealed that PHB1 interacted with STAT3 and with activated STAT3 phosphorylated at Ser727 but not at Tyr705. Knocking down PHB1 with specific short hairpin RNAs attenuated both STAT3 and IL-17 expression levels as well as IL-17 secretion in Th17 cells. These results indicate that PHB1 and STAT3 interact to affect IL-17 secretion in Th17 cells and provide important insights for modulating Th17-mediated pathogenic immune responses.