Eomesodermin Controls Interleukin-5 Production in Memory T Helper 2 Cells through Inhibition of Activity of the Transcription Factor GATA3

SummaryThe regulation of memory CD4+ helper T (Th) cell function, such as polarized cytokine production, remains unclear. Here we show that memory T helper 2 (Th2) cells are divided into four subpopulations by CD62L and CXCR3 expression. All four subpopulations produced interleukin-4 (IL-4) and IL-13, whereas only the CD62LloCXCR3lo population produced IL-5 accompanied by increased H3-K4 methylation at the Il5 gene locus. The transcription factor Eomesodermin (encoded by Eomes) was highly expressed in memory Th2 cells, whereas its expression was selectively downregulated in the IL-5-producing cells. Il5 expression was enhanced in Eomes-deficient cells, and Eomesodermin was shown to interact with the transcription factor GATA3, preventing GATA3 binding to the Il5 promoter. Memory Th2 cell-dependent airway inflammation was attenuated in the absence of the CD62LloCXCR3lo population but was enhanced by Eomes-deficient memory Th2 cells. Thus, IL-5 production in memory Th2 cells is regulated by Eomesodermin via the inhibition of GATA3 activity.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (241 K)Download as PowerPoint slideHighlights► IL-5 producers exist exclusively in the CD62LloCXCR3lo memory Th2 cell subpopulation ► IL-5 expression is controlled by Eomes and chromatin status in memory Th2 cells ► Eomes limits IL-5 expression via inhibition of GATA3 function in memory Th2 cells ► IL-5-producing CD62LloCXCR3lo memory Th2 cells are crucial in airway inflammation