Paracrine IL-2 is required for optimal type 2 effector cytokine production

MR Olson, BJ Ulrich, SA Hummel, I Khan… - The Journal of …, 2017 - journals.aai.org
MR Olson, BJ Ulrich, SA Hummel, I Khan, B Meuris, Y Cherukuri, AL Dent, SC Janga
The Journal of Immunology, 2017journals.aai.org
IL-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 …
Abstract
IL-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.
journals.aai.org