Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen

By M. Caton, Matthew Smith-Raska, B. Reizis. Journal of Experimental Medicine, 2007

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Signaling through Notch receptors and their transcriptional effector RBP-J is essential for lymphocyte development and function, whereas its role in other immune cell types is unclear. We tested the function of the canonical Notch–RBP-J pathway in dendritic cell (DC) development and maintenance in vivo. Genetic inactivation of RBP-J in the bone marrow did not preclude DC lineage commitment but caused the reduction of splenic DC fraction. The inactivation of RBP-J in DCs using a novel DC-specific deleter strain caused selective loss of the splenic CD8− DC subset and reduced the frequency of cytokine-secreting CD8− DCs after challenge with Toll-like receptor ligands. In contrast, other splenic DC subsets and DCs in the lymph nodes and tissues were unaffected. The RBP-J–deficient splenic CD8− DCs were depleted at the postprogenitor stage, exhibited increased apoptosis, and lost the expression of the Notch target gene Deltex1. In the spleen, CD8− DCs were found adjacent to cells expressing the Notch ligand Delta-like 1 in the marginal zone (MZ). Thus, canonical Notch–RBP-J signaling controls the maintenance of CD8− DCs in the splenic MZ, revealing an unexpected role of the Notch pathway in the innate immune system.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/ee73cfe95d1d46803d2b3c127acdebd6add5bf64

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Citations in the corpus

Intestinal lamina propria dendritic cell subsets have different origin and functions. (2009, methodology): “To investigate the latter option, we performed a transfer with a 1:1 mixture of monocytes that yield either green fluorescent lpDCs (Cx3cr1gfp/+ mono- cytes) or red fluorescent lpDCs (CD11c-Cre:R26tdRFP mono- cytes) (Caton et al., 2007; Luche et al., 2007).”
The Cellular and Molecular Origin of Tumor-associated Macrophages (2014, neutral): “In DCs, canonical Notch signaling mediated by the key transcriptional regulator, RBPJ, controls lineage commitment and terminal differentiation (27, 29, 30).”
ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis (2015, background): “…modified mice harboring exon 2 of Xbp1 flanked by two loxP sites (Lee et al., 2008) were crossed with mice expressing Cre recombinase under control of the integrin alpha X (Itgax) promoter (termed CD11c-Cre) (Figures S2A– S2C) that deletes selectively in conventional DCs (Caton et al., 2007).”
Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species (2016, background): “This subset of splenic cDC2s requires Notch2 for their terminal differentiation (Caton et al., 2007; Lewis et al., (A and B) The lineage dimension of the mouse One-SENSE plots includes CAD Siglec-H and B220 as pDC markers.”
IRF4 Transcription Factor-Dependent CD11b+ Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses (2013, background): “crossed the DC-specific Cre recombinase mouse (Itgax-cre) (Caton et al., 2007) with a mouse wherein the Irf4 gene (exons 1 and 2) is flanked by loxP sites and a GFP construct is placed in the reverse orientation, upstream of the Irf4 promoter region (Irf4) (Klein et al.”
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development (2008, methodology): “Consistent with the expected recombination frequency, the PDC population showed a significant 3-fold reduction in the BM of E2-2flox/flox, CD11c-Cre+ CKO mice compared to E2-2wt/wt, CD11c-Cre+ controls (Figure 3E).”
Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages (2012, background): “…viable and are produced at express fluorescent reporters, Cre recombinase, or the diphtheria toxin receptor (DTR) for the purpose of allowing tracking of DCs or to allow the inducible depletion of DCs for functional studies in vivo (Jung et al., 2002; Lindquist et al., 2004; Caton et al., 2007).”
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