Olson, Matthew R.Ulrich, Benjamin J.Hummel, Sarah A.Khan, IbrahimMeuris, BriceCherukur, YesesriDent, Alexander L.Janga, Sarath ChandraKaplan, Mark H.2019-02-182019-02-182017-06-01Olson, M. R., Ulrich, B. J., Hummel, S. A., Khan, I., Meuris, B., Cherukuri, Y., Dent, A. L., Janga, S. C., … Kaplan, M. H. (2017). Paracrine IL-2 Is Required for Optimal Type 2 Effector Cytokine Production. Journal of immunology (Baltimore, Md. : 1950), 198(11), 4352-4359.https://hdl.handle.net/1805/18417IL-2 is a pleiotropic cytokine that promotes the differentiation of Th cell subsets, including Th1, Th2, and Th9 cells, but it impairs the development of Th17 and T follicular helper cells. Although IL-2 is produced by all polarized Th subsets to some level, how it impacts cytokine production when effector T cells are restimulated is unknown. We show in this article that Golgi transport inhibitors (GTIs) blocked IL-9 production. Mechanistically, GTIs blocked secretion of IL-2 that normally feeds back in a paracrine manner to promote STAT5 activation and IL-9 production. IL-2 feedback had no effect on Th1- or Th17-signature cytokine production, but it promoted Th2- and Th9-associated cytokine expression. These data suggest that the use of GTIs results in an underestimation of the presence of type 2 cytokine-secreting cells and highlight IL-2 as a critical component in optimal cytokine production by Th2 and Th9 cells in vitro and in vivo.en-USPublisher PolicyBrefeldin ACell DifferentiationCytokinesInterleukin-2Interleukin-9Lymphocyte ActivationMice, Inbred C57BLMonensinParacrine CommunicationProtein Synthesis InhibitorsProton IonophoresSTAT5 Transcription FactorTh1 CellsTh17 CellsTh2 CellsArticle