Title

miRNAs are required for embryonic development of skin immune cells

Document Type

Conference Proceeding

Publication Date

5-2018

Publication Title

Journal of Investigative Dermatology

Abstract

Skin immune cells, including Langerhans cells (LCs), dendritic epidermal T cells (DETCs), and dermis-resident macrophages (MFs), play an essential role in skin homeostasis and immunity. miRNAs are small, noncoding RNAs regulating immune cell development and function. However, the role of miRNAs in skin immune cell ontogeny remains unclear. Recently, a myeloid lineage reporter, colony stimulating factor 1 receptor (CSF1R) Cre reporter was used to fate map LC precursor and tissue resident MF development. Given that miR-155 is a key miRNA involved in immune response, to study the potential role of miR-155 in embryonic LCs and resident MFs, we created Csf1rCremiR-155GFPmice in which both miR-155 and GFP expressions are induced by Csf1rCre. As expected, the majority of LC precursors and skin-resident MFs highly expressed GFP. Surprisingly, epidermal Vγ3+ DETCs that emerged as early as at E16.5 were all GFP-positive cells, and nearly all fetal thymic γδ T cells were also GFP-positive, even though the overexpression of miR-155 did not significantly disturb embryonic LCs, MFs and γδ T cells. This observation was confirmed by Csf1rCreRosa26EGFP reporter mice, suggesting that CSF1R promoter drives both embryonic myeloid and lymphoid cell lineages. To further study the role of miRNAs in ontogeny of LCs, skin-resident MFs and DETCs, we next generated Csf1rCreDicerf/fKO mice with deficient miRNAs, which led to impaired development of LCs and dermal MFs starting at E18.5. Likewise, DETCs were almost completely eliminated from the KO epidermis and Vγ3+ γδ T cell number was severely reduced in KO fetal thymus, due to the survival and maturation defects of thymic Vγ3+ γδ T cells. Overall, this is the first study to demonstrate that Csf1rCre mice are not only good for fate mapping LCs and resident MFs, but also serve as a new tool for the study of skin-resident γδ T cell embryonic development. Using this model, we have uncovered that miRNAs are critical epigenetic regulators in the ontogeny of skin immune cells.

Volume

138

Issue

5 Suppl S

First Page

S20

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