The basic leucine zipper transcription factor NFIL3 directs the development of a common innate lymphoid cell precursor

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Abstract

Innate lymphoid cells (ILCs) are recently identified lymphocytes that limit infection and promote tissue repair at mucosal surfaces. However, the pathways underlying ILC development remain unclear. Here we show that the transcription factor NFIL3 directs the development of a committed bone marrow precursor that differentiates into all known ILC lineages. NFIL3 was required in the common lymphoid progenitor (CLP), and was essential for the differentiation of αLP, a bone marrow cell population that gives rise to all known ILC lineages. Clonal differentiation studies revealed that CXCR6⁺ cells within the αLP population differentiate into all ILC lineages but not T- and B-cells. We further show that NFIL3 governs ILC development by directly regulating expression of the transcription factor TOX. These findings establish that NFIL3 directs the differentiation of a committed ILC precursor that gives rise to all ILC lineages and provide insight into the defining role of NFIL3 in ILC development.

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Xiaofei Yu

University of Texas Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.
Yuhao Wang

University of Texas Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.
Mi Deng

University of Texas Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.
Yun Li

University of Texas Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.
Kelly A Ruhn

University of Texas Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.
Cheng Cheng Zhang

University of Texas Southwestern Medical Center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.
Lora V Hooper

University of Texas Southwestern Medical Center, Dallas, United States

For correspondence
lora.hooper@utsouthwestern.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal experiments were approved by the Institutional Animal Care and Research Advisory Committee at the University of Texas Southwestern Medical Center, and the approved animal protocol number is 1004-06-04-1. The institutional guidelines for the care and use of laboratory animals were followed.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.