title: The ETS1 transcription factor is required for the development and cytokine-induced expansion of ILC2.
abstract: Group 2 innate lymphoid cells (ILC2s) are a subset of ILCs that play a protective role in the response to helminth infection, but they also contribute to allergic lung inflammation. Here, we report that the deletion of the ETS1 transcription factor in lymphoid cells resulted in a loss of ILC2s in the bone marrow and lymph nodes and that ETS1 promotes the fitness of the common progenitor of all ILCs. ETS1-deficient ILC2 progenitors failed to up-regulate messenger RNA for the E protein transcription factor inhibitor ID2, a critical factor for ILCs, and these cells were unable to expand in cytokine-driven in vitro cultures. In vivo, ETS1 was required for the IL-33-induced accumulation of lung ILC2s and for the production of the T helper type 2 cytokines IL-5 and IL-13. IL-25 also failed to elicit an expansion of inflammatory ILC2s when these cells lacked ETS1. Our data reveal ETS1 as a critical regulator of ILC2 expansion and cytokine production and implicate ETS1 in the regulation of Id2 at the inception of ILC2 development.
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, IL 60637.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Zook
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, IL 60637.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ramirez
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, IL 60637.
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Grant
authors.initials: G
authors.lastname: van der Voort
authors.affiliation: Experimental Hematopoiesis Unit, Department of Clinical and Experimental Medicine, Faculty of Medicine for Health Sciences, Linköping University, 58183 Linköping, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Sigvardsson
authors.affiliation: Department of Medicine, Section of Cardiology, The University of Chicago, Chicago, IL 60637.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Svensson
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, IL 60637 Department of Pathology, The University of Chicago, Chicago, IL 60637.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, IL 60637 Department of Pathology, The University of Chicago, Chicago, IL 60637 bkee@bsd.uchicago.edu.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Kee
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; C494042:Ets1 protein, mouse; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D050784:Proto-Oncogene Protein c-ets-1