Role of BATF in the Development of Innate Lymphoid Cells Elucidated

By Lynn McCain | 10 February

ILC deficiency leads to defective secondary lymphoid tissue development in Batf-/- mice. The size and numbers of Peyer’s patches in adult WT and Batf-/- mice are shown along with frequencies of LTi cells in WT and Batf-/- fetal tissues at embryonic day 13.5-14.5.  A series of sophisticated processes are required in the development of innate lymphoid cells (ILC) for them to reach maturity. The Kim laboratory discovered that basic leucine zipper ATF-like transcription factor (Batf) regulates the production of ILC progenitors in the bone marrow as well as the maintenance of ILCs in the periphery. These cells are strategically distributed in peripheral tissues to provide important innate immunity to fight pathogens such as pathogenic viruses and bacteria.

Batf expression is induced during ILC development at the α-lymphoid progenitor stage in response to cytokine IL-17. 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, which can result in allergies, asthma, and autoimmune diseases; and defective immunity to enteric bacterial infections, which could lead to irritable bowel syndrome and other GI disorders. Thus, concludes Liu et al, Batf plays critical roles in bone marrow hematopoiesis, peripheral homeostasis, and effector functions of ILCs.

The full publication in the American Association for the Advancement of Science's Immunology can be read here.

BATF regulates innate lymphoid cell hematopoiesis and homeostasis
Qingyang LiuMyung H KimLeon FriesenChang H Kim. Sci Immunol. 2020 Dec 4;5(54):eaaz8154.  
doi: 10.1126/sciimmunol.aaz8154. PMID: 33277375.

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