Cell type–specific actions of Bcl11b in early T-lineage and group 2 innate lymphoid cells

Abstract

The zinc finger transcription factor, Bcl11b, is expressed in T cells and group 2 innate lymphoid cells (ILC2s) among hematopoietic cells. In early T-lineage cells, Bcl11b directly binds and represses the gene encoding the E protein antagonist, Id2, preventing pro-T cells from adopting innate-like fates. In contrast, ILC2s co-express both Bcl11b and Id2. To address this contradiction, we have directly compared Bcl11b action mechanisms in pro-T cells and ILC2s. We found that Bcl11b binding to regions across the genome shows distinct cell type–specific motif preferences. Bcl11b occupies functionally different sites in lineage-specific patterns and controls totally different sets of target genes in these cell types. In addition, Bcl11b bears cell type–specific post-translational modifications and organizes different cell type–specific protein complexes. However, both cell types use the same distal enhancer region to control timing of Bcl11b activation. Therefore, although pro-T cells and ILC2s both need Bcl11b for optimal development and function, Bcl11b works substantially differently in these two cell types.

Severe and multifaceted systemic immunosuppression caused by experimental cancers of the central nervous system requires release of non-steroid soluble mediators

“…We found that Rag1 and Rag2 genes, TCF3, TCF7, Gata3, and BCl11b, and Notch 1 were downregulated in thymi of GL261 tumor-bearing mice compared to controls ( Figure 3 D and S1 D). Downregulation of these genes can be consistent with a block between DN2-DN3 transition ( Figure 2 and (52,53,69,70)). Interestingly, another significantly downregulated gene in thymi of GL261-bearing mice compared to controls was Coro1a (Figure 3 Gene expression during experimental GBM induced thymic involution is not consistent with a stress response.…”

Activation of group 2 innate lymphoid cells alleviates aging-associated cognitive decline

“…LC2/b6 line is an immortalized ILC2 cell line that exhibits the molecular and functional properties of activated ILC2 (Zhang et al, 2017). The transcriptome and functional capability of LC2/b6 cell lines were extensively characterized by our recent work (Hosokawa et al, 2019; Shen et al, 2019; Zhang et al, 2017). ILC2/b6 cells express all known ILC2 signature genes (Hosokawa et al, 2019; Shen et al, 2019; Zhang et al, 2017).…”

“…The transcriptome and functional capability of LC2/b6 cell lines were extensively characterized by our recent work (Hosokawa et al, 2019; Shen et al, 2019; Zhang et al, 2017). ILC2/b6 cells express all known ILC2 signature genes (Hosokawa et al, 2019; Shen et al, 2019; Zhang et al, 2017). They vigorously produce IL-5 and IL-13 in vitro and lack the production of IL-17, IL-22, IFN-γ, or other cytokines characteristic of the alternative lineage (Hosokawa et al, 2019; Shen et al, 2019; Zhang et al, 2017).…”

“…ILC2/b6 cells express all known ILC2 signature genes (Hosokawa et al, 2019; Shen et al, 2019; Zhang et al, 2017). They vigorously produce IL-5 and IL-13 in vitro and lack the production of IL-17, IL-22, IFN-γ, or other cytokines characteristic of the alternative lineage (Hosokawa et al, 2019; Shen et al, 2019; Zhang et al, 2017). Lentiviral transduction was performed with cultured ILC2/b6 cells, as we previously described (Hosokawa et al, 2019; Shen et al, 2019).…”

“…They vigorously produce IL-5 and IL-13 in vitro and lack the production of IL-17, IL-22, IFN-γ, or other cytokines characteristic of the alternative lineage (Hosokawa et al, 2019; Shen et al, 2019; Zhang et al, 2017). Lentiviral transduction was performed with cultured ILC2/b6 cells, as we previously described (Hosokawa et al, 2019; Shen et al, 2019). GFP + cells were sorted by fluorescence-activated cell sorting, and 10 5 cells were transferred into aged mice by i.c.v.…”