BATF Acts As an Essential Regulator of IL-25-responsive Migratory ILC2 Cell Fate and Function

Overview

Journal Sci Immunol

Specialty Allergy & Immunology

Date 2020 Jan 12

PMID 31924686

Citations 45

Authors

Mindy M Miller

Preeyam S Patel

Katherine Bao

Thomas Danhorn

Brian P OConnor

R Lee Reinhardt

Affiliations

Soon will be listed here.

Abstract

A transitory, interleukin-25 (IL-25)-responsive, group 2 innate lymphoid cell (ILC2) subset induced during type 2 inflammation was recently identified as iILC2s. This study focuses on understanding the significance of this population in relation to tissue-resident nILC2s in the lung and intestine. RNA-sequencing and pathway analysis revealed the AP-1 superfamily transcription factor BATF (basic leucine zipper transcription factor, activating transcription factor-like) as a potential modulator of ILC2 cell fate. Infection of BATF-deficient mice with showed a selective defect in IL-25-mediated helminth clearance and a corresponding loss of iILC2s in the lung characterized as IL-17RB, KLRG1, BATF, and Arg1 BATF deficiency selectively impaired iILC2s because it had no impact on tissue-resident nILC2 frequency or function. Pulmonary-associated iILC2s migrated to the lung after infection, where they represented an early source of IL-4 and IL-13. Although the composition of ILC2s in the small intestine was distinct from those in the lung, their frequency and IL-13 expression remained dependent on BATF, which was also required for optimal goblet and tuft cell hyperplasia. Findings support IL-25-responsive ILC2s as early sentinels of mucosal barrier integrity.

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