Myc binding protein 2 suppresses M2‐like phenotypes in macrophages during zymosan‐induced inflammation in mice

Abstract

MYCBP2 is an E3 ubiquitin ligase, which is well characterized as a key element in the inhibition of neuronal growth, synapse formation and synaptic strength by regulating several signaling pathways. Although MYCBP2 was suspected to be expressed also in immune cells, to date nothing is known about its role in inflammation. We used Multi-epitope ligand cartography (MELC), a method for multiple sequential immunohistology, to show that MYCBP2 is strongly expressed in monocyte-derived macrophages during zymosan-induced inflammation. We generated a myeloid-specific knockout mouse and found that loss of MYCBP2 in myeloid cells reduced nociceptive (painful) behavior during the resolution phase (1-3 days after zymosan injection). Quantitative MELC analyses and flow cytometric analysis showed an increased number of CD206-expressing macrophages in the inflamed paw tissue. Fittingly, CD206 and arginase 1 expression was upregulated in MYCBP2-deficient bone marrow-derived macrophages after polarization with IL10 or IL4. The regulation of protein expression in these macrophages by MYCBP2 varied depending on the polarization signal. The increased IL10-induced CD206 expression in MYCBP2-deficient macrophages was mediated by p38 MAPK, while IL4-induced CD206 expression in MYCBP2-deficient macrophages was mediated by protein kinase A.

Using toponomics to characterize phenotypic diversity in alveolar macrophages from male mice treated with exogenous SP-A1

“…In addition to the information generated about the influence of SP-A on AM, an important aspect of this study was the development of approaches that allowed us to use TIS data to compare multiple samples from the same or different subjects. In previous studies TIS was used as a descriptive tool to characterize one or two samples, and in some cases to do some comparison between tissue sections from different groups of subjects [35][36][37][38][39][40]45]. However, there has not been another study where this many individual cells (> 100) belonging to different experimental groups have been studied and compared.…”

“…1. Although prior studies with TIS, a serial immunostainer, have been largely descriptive and involved detailed analysis of one or two samples, some have done some limited comparisons of whole images of tissue sections [35][36][37][38][39][40]. In this study we investigated the effect of SP-A on AM phenotype using TIS.…”

Role of the Ubiquitin System in Chronic Pain

“…Myc binding protein 2 (MYCBP2) is another E3 ubiquitin ligase, which can inhibit neuron growth and synapse formation by regulating various signaling pathways. Research has proven that its selective deletion in macrophages can reduce zymogeninduced inflammatory pain and promote the resolution of inflammation (Pierre et al, 2018). Other E3 ubiquitin ligases, such as ligand of numb proteins X1/2 (LNX1/LNX2), are functional regulators of neuronal GlyT2.…”

Deletion of an Enhancer in FGF5 is Associated With Ectopic Expression in Goat Hair Follicles and the Cashmere Growth Phenotype

“…The mutations in the SGCB gene can lead to a loss of functional protein and result in limb-girdle muscular dystrophy disease [40]. MYCBP2 is a member of the PHR protein family and an E3 ubiquitin ligase, and it was shown to have important functions in developmental processes, such as axon termination and synapse formation [41]. WARS2 has low enzyme activity, and inhibition of WARS2 in endothelial cells reduces angiogenesis [42,43].…”