Project description:Microarrays were used to determine transcriptional differences between CCR6+ ILC3s isolated from RorccreTnfsf11fl/fl and Tnfsf11fl/fl small intestine lamina propria.
Project description:Microarray was used to determine transcriptional differences between Nr1d1+/+ CCR6+ ILC3s and Nr1d1-/- CCR6+ ILC3s isolated from small intestine lamina propria
Project description: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 produce 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. Lastly, 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.
Project description:ILC3 contain 3 well-defined subsets, CCR6+ ILC3, NKp46+ ILC3, and CCR6–NKp46– DN ILC3. These subsets had not previously been transcriptionally compared and the extent to which they had shared or unique transcriptional profiles remained unclear. We used microarray to determine transcriptional differences between these 3 subsets and to find putative factors that support the survival of CCR6+ ILC3 during cytokine depletion.
Project description: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 produce 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. Lastly, 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.
Project description: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 produce 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. Lastly, 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.
Project description:CCR6+NKp46- ILC3 were isolated from the small intestine of untreated mice by flow cytometry. ILC3 from 3 mice were pooled for subsequent RNA sequencing.
Project description:CCR6+ innate lymphoid cells were sorted from the mesenteric lymph node of naïve C57BL/6 mice Cells were sort purified as lineage negative, CD127+ CD90.2+ CCR6+ ST2- 4 replicates were performed