T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo

Abstract

Innate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Various subsets exist resembling T cell lineages defined by the expression of specific transcription factors. Thus, T-bet is expressed in ILC1 and Th1 cells. In order to further understand the functional roles of T-bet in ILC, we generated a fate-mapping mouse model that permanently marks cells and their progeny that are expressing, or have ever expressed T-bet. Here we have identified and characterised a novel ILC with characteristics of ILC1 and ILC2 that are fate-mapped for T-bet expression and arise early in neonatal life prior to establishment of a mature microbiome. These ILC1-ILC2 cells are critically dependent on T-bet and are able to express type 1 and type 2 cytokines at steady state, but not in the context of inflammation. These findings refine our understanding of ILC lineage regulation and stability and have important implications for the understanding of ILC biology at mucosal surfaces.

Transcription factor-driven regulation of ILC1 and ILC3

“…]. Moreover, preliminary data of fate-mapper and reporter mouse models for T-bet demonstrated that ~5% of intestinal ILC2 express T-bet [ 137 ]. In MLN ILC2, GATA3 appears to bind to an intron in Tbx21 , perhaps resulting from a direct interaction between T-bet and GATA3 as in CD4 + T cells, and perhaps due to the redistribution of GATA3 away from GATA3-target genes [ 79 , 138 ].…”

“Just one word, plastic!”: Controversies and caveats in innate lymphoid cell plasticity

“…Several other unanswered questions and caveats remain in the field of ILC2 plasticity in the lungs. Given that in vitro stimulation of gut ILC2s with IL-12 and IL-18 does not induce the upregulation of T-bet, there is the question of whether phenotypic changes in the lung represent a tissue-specific phenomenon ( 71 ). Indeed, different organs and tissues may be more permissive to induced plasticity or altered transcriptional profiles of a given ILC subset.…”