Dicer-Dependent MicroRNAs Control Maturation, Function, and Maintenance of Langerhans Cells In Vivo

Abstract

Material Supplementary 2.DC1http://www.jimmunol.org/content/suppl/2010/06/04/jimmunol.090391

MicroRNAs Regulate Dendritic Cell Differentiation and Function

“…Given that the average miRNA t 1/2 is ∼5 d (33), and most DCs are shortlived cells, it is likely that the time needed for loss of Dicer to take effect exceeds the DC life span. LCs, however, which have a t 1/2 of several weeks in mice, showed increased turnover and apoptosis, altered surface receptor expression, and a block in the maturation process when lacking Dicer, which rendered them unable to efficiently prime CD4 + T cells (32). Thus, although future attempts to study the global effect of loss of miRNAs in DCs would require an approach other than eliminating Dicer action, the observations in LCs suggest that miRNAs are critical for DC homeostasis and the hallmark Ag presentation and costimulation functions of DCs.…”

Novel insights into the role of immune cells in skin and inducible skin-associated lymphoid tissue (iSALT)

“…e protective role of LCs in CHS by tolerizing CD8 T cells and activating Treg cells has also been demonstrated [34]. Besides, the observations of inducible LC-speci c ablation strategy using Langerin-DTR(diphtheria toxin receptor)-knocked-in mice and of mice lacking LCs due to independent molecular defects show that LCs and dDCs seem to have a functional redundancy [35,36,37,38,39]. Accumulating literatures support the concept that rather the hapten dose determines the requirement for LCs for e cient T cell priming, and the number of skin DCs, but not the type of DCs, regulates the strength of the CHS reaction [31,36,40].…”

Functional regulation of monocyte-derived dendritic cells by microRNAs

“…In hematopoietic cells, T cell-specific Drosha as well as Dicer conditional knockout mice both spontaneously develop lymphoproliferative multi-organ inflammatory disease and die within a few weeks of birth, again indicating that importance of the two enzymes in leukocyte differentiation and function (Chong et al, 2008). In DCs, lineage-specific (CD11c + ) deletion of Dicer caused reduction in langerhans cells without obvious perturbation of other subsets (Kuipers et al, 2010b). Lack of DC phenotypes is proposed to be due to the short life span of resident DCs and long half-life of miRNAs (Kuipers et al, 2010b), it could also be that deletion of Dicer in CD11c + cells is too late to affect DC differentiation from CD11c -precursors.…”

“…In DCs, lineage-specific (CD11c + ) deletion of Dicer caused reduction in langerhans cells without obvious perturbation of other subsets (Kuipers et al, 2010b). Lack of DC phenotypes is proposed to be due to the short life span of resident DCs and long half-life of miRNAs (Kuipers et al, 2010b), it could also be that deletion of Dicer in CD11c + cells is too late to affect DC differentiation from CD11c -precursors. Nevertheless, in vitro manipulation of miRNA expression in DC precursors can change development fate of normal DCs (Kuipers et al, 2010a).…”

“…It remains to be tested whether prevention of miR-146a upregulation during LC differentiation can alter cell fate. At least in mice deficient in miRNA biogenesis by targeting Dicer (Kuipers et al, 2010b) and Drosha in DC lineages (YZ, unpublished), the pool of LCs was severely diminished. Despite the fact that forced expression of miR-146a does not alter developmental fate, it does reduce TLR2-dependent NFκB signaling (Jurkin et al, 2010).…”