2022
DOI: 10.3390/cells11030404
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Multistability in Macrophage Activation Pathways and Metabolic Implications

Abstract: Macrophages are innate immune cells with a dynamic range of reversible activation states including the classical pro-inflammatory (M1) and alternative anti-inflammatory (M2) states. Deciphering how macrophages regulate their transition from one state to the other is key for a deeper understanding of inflammatory diseases and relevant therapies. Common regulatory motifs reported for macrophage transitions, such as positive or double-negative feedback loops, exhibit a switchlike behavior, suggesting the bistabil… Show more

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Cited by 34 publications
(21 citation statements)
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References 160 publications
(209 reference statements)
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“…These phenotypes coincide with those identified in 15 . However, our results also indicate that the number of multi-stabile phenotypes (e.g., quad-stable) in stochastic systems is restricted to bi-and at most tri-stability, which is in accordance with the current literature [23][24][25] . The validity of this hypothesis would have a huge impact on our understanding of macrophage cells and needs to be confirmed.…”
Section: Discussionsupporting
confidence: 92%
“…These phenotypes coincide with those identified in 15 . However, our results also indicate that the number of multi-stabile phenotypes (e.g., quad-stable) in stochastic systems is restricted to bi-and at most tri-stability, which is in accordance with the current literature [23][24][25] . The validity of this hypothesis would have a huge impact on our understanding of macrophage cells and needs to be confirmed.…”
Section: Discussionsupporting
confidence: 92%
“…Detail examination of their GO functional modules revealed that C5 expressed distinct genes of phosphate pentose ( Pgls and Taldo1 ) and purine salvage pathways ( Apert and Hprt ), an indicator M1 state ( Supplemental Data Sheet 2 ). 48 , 49 On the other hand, C30 and expressed genes were involved in de novo purine synthesis, such as Adss , Paics and Impdh2 , an indicator for M2 anti-inflammatory and phagocytic macrophages ( Supplemental Data Sheet 2 ). In addition, both clusters expressed glycolysis- and electron transfer chain-related proteins ( Supplemental Data Sheet 2 ).…”
Section: Resultsmentioning
confidence: 99%
“…The wild-type–specific macrophage C30 also leans toward M2-type, whereas the mutant C5 leans more toward M1 based on their metabolic signatures. 48 , 49 Therefore weaker M2-related phagocytic activity in the mutant vitreous might contribute to the unresolved cells.…”
Section: Discussionmentioning
confidence: 99%
“…Macrophages have different phenotypes with unique functions during wound healing and their transition from M1-phenotype to M2-phenotype can be easily achieved by different inflammatory cytokines, including IL-4, IL-10, or IL-13, and various pathways of signal transduction, transcriptional and post-transcriptional regulatory networks, such as miRNAS, e.g., miR-27a-5p, let-7c-1-3p, and lncRNAS, e.g., lncFAO, lnc XIST, and lnc GAS5 [ 15 , 37 , 38 , 39 ] ( Figure 5 ).…”
Section: Discussionmentioning
confidence: 99%