MiRNAs are required for embryonic development of Langerhans Cells

Document Type

Conference Proceeding

Publication Date


Publication Title

J Immunol


Langerhans cells (LCs) are epidermal-resident dendritic cells that play important roles in skin immunity and tolerance. Recent fate-mapping studies have demonstrated that adult LCs derive predominantly from fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. However, the role of epigenetic regulations in embryonic development of LCs remains unclear. MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression of their mRNA targets. We and others recently reported that miRNAs are key players in regulating immune cell development and function, including LCs. To further study the role of miRNAsin LC ontogeny, we generated CSF1r Dicer KO mice in which miRNAs aredeficient in myeloid lineage cells including LCs. As expected, the frequency of LCs was drastically reduced in Dicer KO adult mice. Interestingly, there was also a significant reduction (p=0.027) of epidermal LCs in Dicer KO embryos at E18.5, suggesting that miRNAs are crucial for embryonic development of LCs. Given the differential expression of miR-150 and miR- 155 in embryonic LC development, we generated CSF1r miR-150 KI and CSF1r miR-155 KI mice in which expression of miR-150 and miR-155 is upregulated in LC-lineage, respectively. Surprisingly, neither strain caused defective LC development in fetal or adult epidermis. Overall, this is the first study to demonstrate that miRNAs are required for embryonic LC development. Furthermore, although overexpression of miR-150 or miR-155 is dispensable for LC ontogeny, the specific miRNAs responsible for proper LC development deserve to be further explored.




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