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Deletion of microRNA miR-223 increases Langerhans cell cross-presentation
Qing-Sheng Mi1, Ying-Ping Xu, He Wang
1Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United States. qmi1@hfhs.org
Insights
MicroRNA miR-223 negatively regulates Langerhans cell (LC) cross-presentation. While its absence doesn't affect LC development or homeostasis, it enhances antigen-specific CD8(+) T cell proliferation.
Area of Science:
- Immunology
- Molecular Biology
- Dermatology
Background:
- Langerhans cells (LCs) are crucial skin immune cells.
- MicroRNAs (miRNAs) regulate cellular functions, but individual roles in LCs are unclear.
- miR-223 is expressed in myeloid cells and highly in epidermal LCs.
Purpose of the Study:
- To investigate the role of miR-223 in regulating the development and function of epidermal LCs.
- To determine if miR-223 impacts LC homeostasis, maturation, migration, and antigen presentation.
Main Methods:
- Utilized miR-223 knockout (KO) mice and wild-type (WT) littermates.
- Assessed LC number, maturation, migration, and phagocytic capacity.
- Evaluated LC-mediated antigen-specific CD8(+) and CD4(+) T cell proliferation in vitro and in vivo.
Main Results:
- LC number, maturation, migration, and phagocytosis were similar between miR-223 KO and WT mice.
- Lack of miR-223 significantly enhanced LC cross-presentation of antigens to CD8(+) T cells.
- miR-223 deficiency did not affect LC stimulation of CD4(+) T cells.
Conclusions:
- miR-223 negatively regulates the cross-presentation function of Langerhans cells.
- miR-223 is not essential for the basic homeostasis and development of LCs.
- This finding highlights a specific regulatory role for miR-223 in adaptive immunity mediated by LCs.
Abstract:
Langerhans cells (LCs) are skin-residential dendritic cells that regulate skin immunity. MicroRNAs (miRNAs) are key regulators in the control of biological functions in a variety of cell types. Deletion of all miRNAs interrupts the homeostasis and function of epidermal LCs. However, the roles of individual miRNAs in regulating LC development and function are still completely unknown. MiRNA miR-223 is especially expressed in the myeloid compartment. Here, we reported that miR-223 is highly expressed in freshly isolated epidermal LCs, and tested whether miR-223 regulates LC development and function using miR-223 knockout (KO) mice. We found that the number, maturation, migration and phagocytic capacity of LCs were comparable between miR-223KO and wild-type mice. However, lack of miR-223 significantly increases LCs-mediated antigen-specific CD8(+) T cell proliferation in vivo and in vitro, while LCs from KO and WT mice showed comparable stimulation for antigen-specific CD4(+) T cells. Our data suggest that miR-223 negatively regulates LC cross-presentation, but may not be required for normal LC homeostasis and development.
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