title: BATF Modulates the Th2 Locus Control Region and Regulates CD4+ T Cell Fate during Antihelminth Immunity.
abstract: The AP-1 factor basic leucine zipper transcription factor, ATF-like (BATF) is important for CD4+Th17, Th9, and follicular Th cell development. However, its precise role in Th2 differentiation and function remains unclear, and the requirement for BATF in nonallergic settings of type-2 immunity has not been explored. In this article, we show that, in response to parasitic helminths, Batf-/-mice are unable to generate follicular Th and Th2 cells. As a consequence, they fail to establish productive type-2 immunity during primary and secondary infection. Batf-/-CD4+T cells do not achieve type-2 cytokine competency, which implies that BATF plays a key role in the regulation of IL-4 and IL-13. In contrast to Th17 and Th9 cell subsets in which BATF binds directly to promoter and enhancer regions to regulate cytokine expression, our results show that BATF is significantly enriched at Rad50 hypersensitivity site (RHS)6 and RHS7 of the locus control region relative to AP-1 sites surrounding type-2 cytokine loci in Th2 cells. Indeed, Batf-/-CD4+T cells do not obtain permissive epigenetic modifications within the Th2 locus, which were linked to RHS6 and RHS7 function. In sum, these findings reveal BATF as a central modulator of peripheral and humoral hallmarks of type-2 immunity and begin to elucidate a novel mechanism by which it regulates type-2 cytokine production through its modification of the Th2 locus control region.
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors: Katherine
authors: K
authors: Bao
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors: Tiffany
authors: 0000-0001-8940-3700
authors: T
authors: Carr
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors: Jianxuan
authors: J
authors: Wu
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors: William
authors: W
authors: Barclay
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors: Jingxiao
authors: J
authors: Jin
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710; and.
authors: Maria
authors: M
authors: Ciofani
authors: Department of Biomedical Research, National Jewish Health, Denver, CO 80206 reinhardtl@njhealth.org.
authors: R Lee
authors: 0000-0001-7798-9732
authors: RL
authors: Reinhardt
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D017766:Acid Anhydride Hydrolases; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic / Q000276:immunology*; D019901:Locus Control Region / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D004268:DNA-Binding Proteins; D017766:Acid Anhydride Hydrolases; C495198:Rad50 protein, mouse