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Immunity. 2015 Aug 18;43(2):354-68. doi: 10.1016/j.immuni.2015.07.005. Epub 2015 Jul 28.

Transcription Factor Bcl11b Controls Identity and Function of Mature Type 2 Innate Lymphoid Cells.

Author information

1
Center for Immunology and Microbial Disease, Albany Medical Center, 47 New Scotland Avenue, MC-165, Albany, NY 12208, USA.
2
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.
3
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
T-Cell Biology and Development Section, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
5
Wadsworth Center, New York State Department of Health, Albany, NY 12208, USA.
6
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.

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.

PMID:
26231117
PMCID:
PMC4657441
DOI:
10.1016/j.immuni.2015.07.005
[Indexed for MEDLINE]
Free PMC Article

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