title: Transcription Factor Bcl11b Controls Identity and Function of Mature Type 2 Innate Lymphoid Cells.
abstract: Type 2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Here, we report that Bcl11b, previously considered a T-cell-specific transcription factor, acted directly upstream of the key ILC2 transcription factor Gfi1 to maintain its expression in mature ILC2s. Consequently, Bcl11b(-/-) ILC2s downregulated Gata3 and downstream genes, including Il1rl1 (encoding IL-33 receptor), and upregulated Rorc and type 3 ILC (ILC3) genes. Additionally, independent of Gfi1, Bcl11b directly repressed expression of the gene encoding the ILC3 transcription factor Ahr, further contributing to silencing of ILC3 genes in ILC2s. Thus, Bcl11b(-/-) ILC2s lost their functions and gained ILC3 functions, and although they expanded in response to the protease allergen papain, they produced ILC3 but not ILC2 cytokines and caused increased airway infiltration of neutrophils instead of eosinophils. Our results demonstrate that Bcl11b is more than just a T-cell-only transcription factor and establish that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical Center, 47 New Scotland Avenue, MC-165, Albany, NY 12208, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Califano
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical Center, 47 New Scotland Avenue, MC-165, Albany, NY 12208, USA; Department of Medicine, College of Medicine, University of Florida, 1600 Southwest Archer Road, MSB, Gainesville, FL 32610-0225, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Cho
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical Center, 47 New Scotland Avenue, MC-165, Albany, NY 12208, USA; Department of Medicine, College of Medicine, University of Florida, 1600 Southwest Archer Road, MSB, Gainesville, FL 32610-0225, USA.
authors.forename: Mohammad N
authors.initials: MN
authors.lastname: Uddin
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical Center, 47 New Scotland Avenue, MC-165, Albany, NY 12208, USA; Department of Medicine, College of Medicine, University of Florida, 1600 Southwest Archer Road, MSB, Gainesville, FL 32610-0225, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Lorentsen
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: T-Cell Biology and Development Section, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical Center, 47 New Scotland Avenue, MC-165, Albany, NY 12208, USA; Department of Medicine, College of Medicine, University of Florida, 1600 Southwest Archer Road, MSB, Gainesville, FL 32610-0225, USA. Electronic address: dorina.avram@medicine.ufl.edu.
authors.forename: Dorina
authors.initials: D
authors.lastname: Avram
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D044082:Citrobacter rodentium / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D007113:Immunity, Innate; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016131:Lymphocyte Subsets / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D000072179:Interleukin-1 Receptor-Like 1 Protein; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; D018123:Receptors, Interleukin; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C484722:Ahr protein, mouse; C511143:Bcl11b protein, mouse; C494748:Gata3 protein, mouse; C079873:Gfi1 protein, mouse; C486189:Il1rl1 protein, mouse; C539901:Rorc protein, mouse