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CD163-L1 is an endocytic macrophage protein strongly regulated by mediators in the inflammatory response
Jesper B Moeller1, Marianne J Nielsen, Martin P Reichhardt
1Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.
Insights
CD163-L1, a scavenger receptor, is expressed on macrophages and internalizes via a clathrin pathway. Unlike CD163, it lacks known ligand affinity, suggesting a role in inflammation resolution.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD163-L1 is a scavenger receptor cysteine-rich family member, related to the hemoglobin scavenger receptor CD163.
- Its evolutionary origin involved gene duplication of CD163.
- Understanding CD163-L1's expression and function is crucial for macrophage biology.
Purpose of the Study:
- To characterize the expression pattern and cellular localization of CD163-L1.
- To investigate the regulation of CD163-L1 expression by cytokines and inflammatory mediators.
- To determine the endocytic mechanism and ligand-binding properties of CD163-L1.
Main Methods:
- Immunohistochemistry to assess CD163-L1 expression and colocalization.
- Monocyte culture and differentiation with M-CSF stimulation.
- Treatment with cytokines (IL-6, IL-10, IL-4, IL-13) and inflammatory stimuli (TNF-α, LPS/IFN-γ).
- Confocal microscopy and biochemical assays to study endocytosis and ligand binding.
Main Results:
- CD163-L1 is highly expressed on macrophages, distinct from monocytes, and shows differential expression in tissue macrophages.
- Expression is upregulated by M-CSF, IL-6, and IL-10, but suppressed by IL-4, IL-13, TNF-α, and LPS/IFN-γ.
- CD163-L1 functions as an endocytic receptor internalizing via a clathrin-mediated pathway, independent of cross-linking.
- CD163-L1 lacks measurable affinity for known CD163 ligands like haptoglobin-hemoglobin and bacteria.
Conclusions:
- CD163-L1 shares structural and regulatory similarities with CD163 but differs in ligand specificity and tissue distribution.
- Its distinct expression and endocytic function suggest a unique role for CD163-L1.
- CD163-L1 is postulated to act as a scavenger receptor involved in the resolution of inflammation.
Abstract:
CD163-L1 belongs to the group B scavenger receptor cysteine-rich family of proteins, where the CD163-L1 gene arose by duplication of the gene encoding the hemoglobin scavenger receptor CD163 in late evolution. The current data demonstrate that CD163-L1 is highly expressed and colocalizes with CD163 on large subsets of macrophages, but in contrast to CD163 the expression is low or absent in monocytes and in alveolar macrophages, glia, and Kupffer cells. The expression of CD163-L1 increases when cultured monocytes are M-CSF stimulated to macrophages, and the expression is further increased by the acute-phase mediator IL-6 and the anti-inflammatory mediator IL-10 but is suppressed by the proinflammatory mediators IL-4, IL-13, TNF-α, and LPS/IFN-γ. Furthermore, we show that CD163-L1 is an endocytic receptor, which internalizes independently of cross-linking through a clathrin-mediated pathway. Two cytoplasmic splice variants of CD163-L1 are differentially expressed and have different subcellular distribution patterns. Despite its many similarities to CD163, CD163-L1 does not possess measurable affinity for CD163 ligands such as the haptoglobin-hemoglobin complex or various bacteria. In conclusion, CD163-L1 exhibits similarity to CD163 in terms of structure and regulated expression in cultured monocytes but shows clear differences compared with the known CD163 ligand preferences and expression pattern in the pool of tissue macrophages. We postulate that CD163-L1 functions as a scavenger receptor for one or several ligands that might have a role in resolution of inflammation.
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