Published in

Rockefeller University Press, Journal of Experimental Medicine, 4(220), 2023

DOI: 10.1084/jem.20220440



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Cell autonomous expression of BCL6 is required to maintain lineage identity of mouse CCR6+ ILC3s

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Innate lymphoid cells (ILC) are similar to T helper (Th) cells in expression of cytokines and transcription factors. For example, RORγt is the lineage-specific transcription factor for both ILC3 and Th17 cells. However, the ILC counterpart for BCL6-expressing T follicular helper (Tfh) cells has not been defined. Here, we report that in the ILC compartment, BCL6 is selectively co-expressed with not only CXCR5 but also RORγt and CCR6 in ILC3 from multiple tissues. BCL6-deficient ILC3 produces enhanced levels of IL-17A and IL-22. More importantly, phenotypic and single-cell ATAC-seq analysis show that absence of BCL6 in mature ILC3 increases the numbers of ILC1 and transitional cells co-expressing ILC3 and ILC1 marker genes. A lineage-tracing experiment further reveals BCL6+ ILC3 to ILC1 trans-differentiation under steady state. Finally, microbiota promote BCL6 expression in colonic CCR6+ ILC3 and thus reinforce their stability. Collectively, our data have demonstrated that CCR6+ ILC3 have both Th17 and Tfh programs and that BCL6 expression in these cells functions to maintain their lineage identity.