Research ArticleINNATE LYMPHOID CELLS

BATF regulates innate lymphoid cell hematopoiesis and homeostasis

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Science Immunology  04 Dec 2020:
Vol. 5, Issue 54, eaaz8154
DOI: 10.1126/sciimmunol.aaz8154

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A path to innate lymphoid cells

Mature innate lymphoid cell (ILC) subsets develop from ILC progenitors that have differentiated from early hematopoietic progenitors, but the regulation of this process is not well understood. Liu et al. show that basic leucine zipper ATF-like transcription factor (Batf) is a critical regulator of ILC development. IL-7 induces Batf expression in α-lymphoid progenitors, and Batf activates transcription of the Nfil3 gene, which induces ILC hematopoiesis. The presence of Batf is needed for maintenance of early and late ILC bone marrow progenitors and peripheral homeostasis of ILC1, ILC2, ILC3, and NK cells. Batf deficiency is associated with ILC lymphopenia and defective ILC responses, including inflammation and inadequate protection against enteric bacteria. These findings define the critical role of Batf in ILC development.

Abstract

Early hematopoietic progenitors undergo sophisticated developmental processes to become committed innate lymphoid cell (ILC) progenitors and ultimately mature ILC subsets in the periphery. Basic leucine zipper ATF-like transcription factor (Batf) plays important roles in lymphocyte biology. We report here that Batf regulates the production of bone marrow ILC progenitors and maintenance of peripheral ILCs. The expression of Batf is induced during ILC development at the α-lymphoid progenitor stage in response to the cytokine IL-7. As a potential mechanism, up-regulated Batf binds and activates transcription of the Nfil3 gene to promote ILC hematopoiesis. Batf is necessary to maintain normal numbers of early and late ILC progenitors in the bone marrow and mature ILC1, ILC2, ILC3, and NK cells in most peripheral tissues. Batf deficiency causes ILC lymphopenia, leading to defective ILC responses to inflammatory cytokines and defective immunity to enteric bacterial infections. Thus, Batf plays critical roles in bone marrow hematopoiesis, peripheral homeostasis, and effector functions of ILCs.

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