title: Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3.
abstract: The 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 CD62L(lo)CXCR3(lo) 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 CD62L(lo)CXCR3(lo) 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.
authors: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors: Yusuke
authors: Y
authors: Endo
authors: Chiaki
authors: C
authors: Iwamura
authors: Makoto
authors: M
authors: Kuwahara
authors: Akane
authors: A
authors: Suzuki
authors: Kaoru
authors: K
authors: Sugaya
authors: Damon J
authors: DJ
authors: Tumes
authors: Koji
authors: K
authors: Tokoyoda
authors: Hiroyuki
authors: H
authors: Hosokawa
authors: Masakatsu
authors: M
authors: Yamashita
authors: Toshinori
authors: T
authors: Nakayama
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D050990:GATA3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression; D007156:Immunologic Memory / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis*; D019041:L-Selectin / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D054367:Receptors, CXCR3 / Q000378:metabolism; D012137:Respiratory System / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D000098815:T-bet Transcription Factor
chemical_list: C491198:Eomes protein, mouse; D050990:GATA3 Transcription Factor; D015848:Interleukin-5; D054367:Receptors, CXCR3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D019041:L-Selectin