Nature Immunol type I cytokines cooperate to promote the body's inflammatory response

By | November in Cells at Work Monocytes Monocytes are myeloid cells derived from the bone marrow and play an important role in the maintenance of tissue homeostasis and the inflammatory response
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Monocytes include two groups: classical monocytes, which are infiltrated in inflammatory tissues, and non-classical monocytes, which are patrolmen in the blood
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The main difference between these two subgroups is the level of Ly6 expression [1-2]
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In steady state, classical monocytes with high Ly6 expression can differentiate into tissue-resident macrophages; during tissue inflammation, classical monocytes with high Ly6 expression are rapidly recruited from the systemic circulation and the bone marrow to the site of inflammation and differentiate into effector cells derived from monocytes, a process known as monocyte-to-phagocyte transition (MTPT)
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However, how the process of MTPT is carried out and what role cytokines play in it are still unclear
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Recently, the research group of Burkhard Becher of the University of Zurich in Switzerland published an article in Nature Immunology IFNγ and GM-CSF control complementary differentiation programs in the monocyte-tophagocyte transition during neuroinflammation, and found that the type I cytokine interferon IFNγ and granulocyte macrophage colony stimulating factor GM-CSF complementation controls the differentiation program of MTPT during neuroinflammation
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To study this process, the authors used an experimental allergic encephalomyelitis (EAE) mouse model and isolated skin draining lymph nodes and central nervous system using enzyme-linked immunosorbent assay and high-parameter flow cytometry Cytometry measures the expression of IFNγ and GM-CSF in tissue lysates (Figure 1)
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The authors found that these two effectors have different expression profiles in the skin draining lymph nodes and in the central nervous system, indicating that different tissue sources have an important impact on the monocyte differentiation program, and the monocyte differentiation process has tissue environment specificity
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Figure 1 Measurement of IFNγ and GM-CSF expression in EAE mouse model During the progression of the EAE mouse model, the authors examined cell subsets in the mouse central nervous system by the expression of Ly6C, MHCII, CD11c and MerTK.
expression to differentiate between different cell types
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The authors found that cells with high Ly6C expression could differentiate into MerTK-expressing phagocytes
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To understand the process of monocyte differentiation, the authors then performed single-cell RNA-sequencing to trace cell fate by RNA velocity and reconstruct the developmental direction of cells
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The authors found that only classical monocytes with high Ly6C expression were able to undergo the cell-fate transition process of MTPT
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These data suggest that during the progression of chronic neuroinflammation, the MTPT process occurs in the central nervous system, and classical monocytes with high Ly6C expression accumulate at the site of inflammation through terminally differentiated inflammatory macrophages
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Through gene knockout experiments, the authors demonstrated that IFNγ is a key factor driving the MTPT process, and GM-CSF supports the terminal differentiation of monocytes.
Type I cytokines work together to promote the body's fight against inflammation
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Figure 2.
IFN drives the MTPT process and GM-CSF supports the final differentiation of monocytes.
In general, this work found that, through genetic fate mapping, gene targeting and high-dimensional single-cell multi-omics analysis, Ly6C-highly expressed monocytes In nuclear cells, IFNγ is essential for the gradual acquisition of a mature inflammatory phagocytic phenotype, while GM-CSF is responsible for the production, phagocytosis, and oxidative rupture of interleukins that activate phagocytic function
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These results suggest that pro-inflammatory cytokines guide the MTPT process in the inflammatory central nervous system, providing a new reference for the working mechanism of the immune system
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Original link: https://doi.
org/10.
1038/s41590-021-01117-7 Publisher: Eleven References 1.
Hoeffel, G.
& Ginhoux, F.
Fetal monocytes and the origins of tissue-resident macrophages.
Cell .
Immunol.
330, 5–15 (2018).
2.
Ginhoux, F.
& Guilliams, M.
Tissue-resident macrophage ontogeny and homeostasis.
Immunity 44, 439–449 (2016) Notes for reprinting [Original article] BioArt original article, Personal forwarding and sharing are welcome.
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