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      BATF3 is sufficient for the induction of Il9 expression and can compensate for BATF during Th9 cell differentiation

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          Th9 cells preferentially produce IL-9 and participate in allergic responses and asthma. Differentiation of Th9 cells is induced by IL-4 and TGF-β, and then the cells are amplified by OX40 signals. The transcription factors PU.1, IRF4, and BATF are required for Th9 differentiation. BATF3 is an AP-1 family transcription factor that is highly homologous to BATF; however, its role in Th9 cells is poorly defined. Here, we show that OX40 signaling induced the expression of Batf3 and that its overexpression in the presence or absence of OX40 signaling increased the expression of IL-9 in Th9 cells. BATF3 physically interacted with IRF4 and was bound to the Il9 locus. A transient reporter assay revealed that the BATF3–IRF4 complex induced Il9 promoter activity. BATF3 rescued Il9 expression and restored the capacity to induce the airway inflammation in Batf KO Th9 cells. Thus, BATF3 itself is sufficient for the induction of Th9 cell differentiation and can substitute for BATF during Th9 cell differentiation.

          Immunology: fanning the fires of airway inflammation

          A protein that regulates gene expression in immune cells may contribute to airway inflammation in asthma and allergies. A subset of immune cells known as Th9 cells plays a prominent role in these respiratory disorders, and researchers led by Gap Ryol Lee at Sogang University in Seoul, South Korea, set out to characterize signaling mechanisms that promote Th9 production. They focused specifically on a protein called BATF3, which regulates genes responsible for maturation of a variety of other immune cell types, but whose role with regard to Th9 is poorly understood. They determined that BATF3 has a potent effect in terms of inducing Th9 cell activity, and can even take the place of another known Th9-inducing protein. These findings could assist in the development of treatments that keep airway-constricting inflammation in check.

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          Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity.

          Although in vitro observations suggest that cross-presentation of antigens is mediated primarily by CD8alpha+ dendritic cells, in vivo analysis has been hampered by the lack of systems that selectively eliminate this cell lineage. We show that deletion of the transcription factor Batf3 ablated development of CD8alpha+ dendritic cells, allowing us to examine their role in immunity in vivo. Dendritic cells from Batf3-/- mice were defective in cross-presentation, and Batf3-/- mice lacked virus-specific CD8+ T cell responses to West Nile virus. Importantly, rejection of highly immunogenic syngeneic tumors was impaired in Batf3-/- mice. These results suggest an important role for CD8alpha+ dendritic cells and cross-presentation in responses to viruses and in tumor rejection.
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            Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset.

            Since the discovery of T helper type 1 and type 2 effector T cell subsets 20 years ago, inducible regulatory T cells and interleukin 17 (IL-17)-producing T helper cells have been added to the 'portfolio' of helper T cells. It is unclear how many more effector T cell subsets there may be and to what degree their characteristics are fixed or flexible. Here we show that transforming growth factor-beta, a cytokine at the center of the differentiation of IL-17-producing T helper cells and inducible regulatory T cells, 'reprograms' T helper type 2 cells to lose their characteristic profile and switch to IL-9 secretion or, in combination with IL-4, drives the differentiation of 'T(H)-9' cells directly. Thus, transforming growth factor-beta constitutes a regulatory 'switch' that in combination with other cytokines can 'reprogram' effector T cell differentiation along different pathways.
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              IRF family of transcription factors as regulators of host defense.

              Interferon regulatory factors (IRFs) constitute a family of transcription factors that commonly possess a novel helix-turn-helix DNA-binding motif. Following the initial identification of two structurally related members, IRF-1 and IRF-2, seven additional members have now been reported. In addition, virally encoded IRFs, which may interfere with cellular IRFs, have also been identified. Thus far, intensive functional analyses have been done on IRF-1, revealing a remarkable functional diversity of this transcription factor in the regulation of cellular response in host defense. Indeed, IRF-1 selectively modulates different sets of genes, depending on the cell type and/or the nature of cellular stimuli, in order to evoke appropriate responses in each. More recently, much attention has also been focused on other IRF family members. Their functional roles, through interactions with their own or other members of the family of transcription factors, are becoming clearer in the regulation of host defense, such as innate and adaptive immune responses and oncogenesis.

                Author and article information

                +82-2-705-8458 ,
                Exp Mol Med
                Exp. Mol. Med
                Experimental & Molecular Medicine
                Nature Publishing Group UK (London )
                27 November 2019
                27 November 2019
                November 2019
                : 51
                : 11
                ISNI 0000 0001 0286 5954, GRID grid.263736.5, Department of Life Science, , Sogang University, ; 35 Baekbeom-ro, Mapo-gu Seoul, 04107 Korea
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

                Funded by: FundRef, National Research Foundation of Korea (NRF);
                Award ID: 2017R1A2B3008621
                Award ID: 2014H1A8A1022457
                Award Recipient :
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                © The Author(s) 2019

                Molecular medicine

                cd4-positive t cells, lymphocyte differentiation


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