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Comparative Analysis of the Transcriptome, Proteome, and miRNA Profile of Kupffer Cells and Monocytes
Andrey Elchaninov1,2, Anastasia Lokhonina1,2, Maria Nikitina3
1Laboratory of Regenerative Medicine, National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov of Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia.
Abstract:
Macrophage populations in most mammalian organs consist of cells of different origin. Resident macrophages originate from erythromyeloid precursors of the yolk sac wall; maintenance of the numbers of such macrophages in postnatal ontogenesis is practically independent of bone marrow haematopoiesis. The largest populations of the resident macrophages of embryonic origin are found in the central nervous system (microglia) and liver (Kupffer cells). In contrast, skin dermis and mucous membranes become predominantly colonized by bone marrow-derived monocytes that show pronounced functional and phenotypic plasticity. In the present study, we compared Kupffer cells and monocytes using the immunophenotype, gene expression profile, proteome, and pool of microRNA. The observed differences did not consider the resident liver macrophages as purely M2 macrophages or state that monocytes have purely M1 features. Monocytes show signs of high plasticity and sensitivity to pathogen-associated molecular patterns (e.g., high levels of transcription for Tlr 2, 4, 7, and 8). In contrast, the resident liver macrophages were clearly involved in the regulation of specific organ functions (nitrogen metabolism, complement system protein synthesis).
Insights
Resident liver macrophages and circulating monocytes have distinct origins and functions. This study reveals key differences in their molecular profiles, highlighting monocytes
Area of Science:
- Immunology
- Cell Biology
Background:
- Most mammalian organs host macrophage populations derived from diverse origins.
- Resident macrophages, like microglia and Kupffer cells, originate from embryonic yolk sac precursors.
- Skin and mucous membrane macrophages are primarily derived from bone marrow monocytes, exhibiting plasticity.
Purpose of the Study:
- To compare Kupffer cells (resident liver macrophages) and circulating monocytes.
- To elucidate functional and phenotypic differences between these two macrophage populations.
- To investigate their distinct molecular profiles, including immunophenotype, gene expression, proteome, and microRNA.
Main Methods:
- Comparative analysis of Kupffer cells and monocytes.
- Assessment of immunophenotype.
- Evaluation of gene expression profiles.
- Proteomic analysis.
- MicroRNA pool analysis.
Main Results:
- Kupffer cells and monocytes do not fit into purely M1 or M2 classifications.
- Monocytes display significant plasticity and responsiveness to pathogen-associated molecular patterns, indicated by high Toll-like receptor (TLR) gene expression.
- Resident liver macrophages are integral to specific organ functions, such as nitrogen metabolism and complement protein synthesis.
Conclusions:
- Kupffer cells and monocytes represent distinct macrophage lineages with specialized roles.
- Monocytes possess a high degree of plasticity, enabling adaptation to various stimuli.
- Resident liver macrophages are specialized for maintaining liver homeostasis and function.
