Characterisation of murine MICL (CLEC12A) and evidence for an endogenous ligand
Elwira Pyz1, Cristal Huysamen, Andrew S J Marshall
1The Institute of Infectious Disease and Molecular Medicine, Division of Immunology, University of Cape Town, Cape Town, South Africa.
Insights
Researchers characterized the murine MICL (monomeric C-type lectin-like receptor) and found it regulates cellular activation. This inhibitory receptor plays a role in immune homeostasis and cellular signaling.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Inhibitory receptors are crucial for controlling cellular activation, maintaining immune homeostasis, and regulating immune responses.
- The human MICL (monomeric C-type lectin-like receptor), also known as CLEC12A, is a heavily glycosylated inhibitory receptor primarily found on myeloid cells.
Purpose of the Study:
- To characterize the murine homolog of MICL (mMICL) and compare its structure and function to the human ortholog (hMICL).
- To investigate the expression patterns of mMICL in various immune cells and tissues.
- To explore the potential role of mMICL in cellular signaling and homeostasis.
Main Methods:
- Characterization of murine MICL (mMICL) structure and glycosylation.
- Functional assays to assess inhibitory phosphatase recruitment upon activation.
- Analysis of mMICL expression on leukocytes following TLR agonist stimulation.
- Development and utilization of monoclonal antibodies for mMICL detection.
- Assessment of mMICL ligand recognition in murine tissues.
Main Results:
- Murine MICL (mMICL) is structurally and functionally similar to human MICL (hMICL) but exists as a dimer and is less glycosylated.
- mMICL recruits inhibitory phosphatases and is downregulated on leukocytes after TLR agonist stimulation, similar to hMICL.
- mMICL is predominantly expressed on myeloid cells but also found on B cells, CD8+ T cells, and NK cells.
- mMICL recognizes an endogenous ligand in various murine tissues, indicating a role in homeostasis.
Conclusions:
- Murine MICL (mMICL) is a functional inhibitory receptor with conserved and distinct features compared to its human counterpart.
- mMICL expression extends beyond myeloid cells to include lymphocytes and NK cells, suggesting broader immune regulatory roles.
- The recognition of an endogenous ligand by mMICL highlights its involvement in maintaining tissue homeostasis and regulating immune cell activity.
Abstract:
Inhibitory receptors are required for the control of cellular activation and they play essential roles in regulating homeostasis and immunity. We previously identified a human inhibitory C-type lectin-like receptor, MICL (CLEC12A), a heavily glycosylated monomer predominantly expressed on myeloid cells. Here we characterise the murine homolog of MICL (mMICL), and demonstrate that the receptor is structurally and functionally similar to the human orthologue (hMICL), although there are some notable differences. mMICL is expressed as a dimer and is not heavily glycosylated; however, like hMICL, the receptor can recruit inhibitory phosphatases upon activation, and is down-regulated on leukocytes following stimulation with selected TLR agonists. Using novel monoclonal antibodies, we demonstrate that, like the human receptor, mMICL is predominantly expressed by myeloid cells. However, mMICL is also expressed by B cells and CD8+ T cells in peripheral blood, and NK cells in the bone marrow. Finally, we show that mMICL recognises an endogenous ligand in a variety of murine tissues, suggesting that the receptor plays a role in homeostasis.
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