Genetic dissection of dendritic cell homeostasis and function: lessons from cell type-specific gene ablation

Abstract

Dendritic cells (DCs) are a heterogeneous cell population of great importance in the immune system. The emergence of new genetic technology utilizing the CD11c promoter and Cre recombinase has facilitated the dissection of functional significance and molecular regulation of DCs in immune responses and homeostasis in vivo. For the first time, this strategy allows observation of the effects of DC-specific gene deletion on immune system function in an intact organism. In this review, we present the latest findings from studies using the Cre recombinase system for cell type–specific deletion of key molecules that mediate DC homeostasis and function. Our focus is on the molecular pathways that orchestrate DC life span, migration, antigen presentation, pattern recognition, and cytokine production and signaling.

Continuous sensing of IFNα by hepatic endothelial cells shapes a vascular antimetastatic barrier

“…Note that by crossing the parental Cre-expressing lines with Rosa26-ZsGreen reporter mice (Madisen et al, 2010) the resultant mice showed specific recombination in most hepatocytes (identified by morphology), and liver fibroblast (GFP + /PDGFRβ + ), with about 98.2 ± 0.72% hepatic stellate cells that co-expressed GFP + and PDGFRβ + signals (Fig S5E,F). Similarly, hepatic DCs (GFP + /CD11c + ) had 94.17 ± 2.16% colocalization with GFP, while the colocalization percentage of F4/80 + KCs or LCMs (GFP + /F4/80 + ) was 78.14 ± 5.03% (Fig S5E ,F) (Bleriot & Ginhoux, 2019;Karmaus & Chi, 2014;Madisen et al, 2010). is smaller than their own (12 ± 0.1 µm), similar to what we previously reported (Catarinella et al, 2016).…”

Dendritic cell SIRT1–HIF1α axis programs the differentiation of CD4 + T cells through IL-12 and TGF-β1

“…To gain insights into the role of SIRT1 in DCs, we generated a CD11c with CD11c-Cre (referred to as SIRT1 CD11c−/− hereafter). In addition to DCs, the expression of CD11c in monocytes/macrophages, neutrophils, and some B cells has also been reported (29,30). To examine the specificity and efficacy of SIRT1 deletion, we isolated various cell populations (indicated in SI Appendix, Fig.…”

Continuous sensing of IFNα by hepatic endothelial cells shapes a vascular antimetastatic barrier

“…Note that by crossing the parental Cre-expressing lines with Rosa26-ZsGreen reporter mice ( Madisen et al, 2010 ) the resultant mice showed specific recombination in most hepatocytes (identified by morphology), and liver fibroblast (GFP + /PDGFRβ + ), with about 98.2 ± 0.72% hepatic stellate cells that co-expressed GFP + and PDGFRβ + signals ( Figure 4—figure supplement 1E, F ). Similarly, hepatic DCs (GFP + /CD11c + ) had 94.17 ± 2.16% colocalization with GFP, while the colocalization percentage of F4/80 + KCs or LCMs (GFP + /F4/80 + ) was 78.14 ± 5.03% ( Figure 4—figure supplement 1E,F ; Blériot and Ginhoux, 2019 ; Karmaus and Chi, 2014 ; Madisen et al, 2010 ). Finally, HECs, including LSECs, (GFP + /CD31 + ) showed 85.3 ± 5.03% colocalization ( Figure 4—figure supplement 1E, F ), with no expression of GFP signals in cells other than CD31 + .…”