Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury

Iwai, Haruki; Ataka, Koji; Suzuki, Hajime; Dhar, Ashis; Kuramoto, Eiichi; Yamanaka, Akira; Goto, Tetsuya

doi:10.1186/s12974-021-02283-z

Cited by 31 publications

(23 citation statements)

References 51 publications

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“…Since they express general cholesterol receptors, like LDLR and VLDLR, they would be capable of taking up cholesterol from the extracellular space, where it might be released from activated macrophages. Macrophages are known for their high cholesterol production, and we and others have shown that they increase in number and migrate into the SGC-neuron unit after injury 13, [53][54][55][56] . At present, however, this remains speculation until more functional data can be obtained.…”

Section: Discussionmentioning

confidence: 88%

Comparative transcriptional analysis of satellite glial cell injury response

et al. 2022

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Background: Satellite glial cells (SGCs) tightly surround and support primary sensory neurons in the peripheral nervous system and are increasingly recognized for their involvement in the development of neuropathic pain following nerve injury. SGCs are difficult to investigate due to their flattened shape and tight physical connection to neurons in vivo and their rapid changes in phenotype and protein expression when cultured in vitro. Consequently, several aspects of SGC function under normal conditions as well as after a nerve injury remain to be explored. The recent advance in single cell RNA sequencing (scRNAseq) technologies has enabled a new approach to investigate SGCs. Methods: In this study we used scRNAseq to investigate SGCs from mice subjected to sciatic nerve injury. We used a meta-analysis approach to compare the injury response with that found in other published datasets. Furthermore, we also used scRNAseq to investigate how cells from the dorsal root ganglion (DRG) change after 3 days in culture. Results: From our meta-analysis of the injured conditions, we find that SGCs share a common signature of 18 regulated genes following sciatic nerve crush or sciatic nerve ligation, involving transcriptional regulation of cholesterol biosynthesis. We also observed a considerable transcriptional change when culturing SGCs, suggesting that some differentiate into a specialised in vitro state while others start resembling Schwann cell-like precursors. Conclusion: By using integrated analyses of new and previously published scRNAseq datasets, this study provides a consensus view of which genes are most robustly changed in SGCs after injury. Our results are available via the Broad Institute Single Cell Portal, so that readers can explore and search for genes of interest.

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Section: Discussionmentioning

confidence: 88%

Comparative transcriptional analysis of satellite glial cell injury response

et al. 2022

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“…Since they express general cholesterol receptors, like LDLR and VLDLR, they would be capable of taking up cholesterol from the extracellular space, where it might be released from activated macrophages. Macrophages are known for their high cholesterol production, and we and others have shown that they increase in number and migrate into the SGCneuron unit after injury (Lu & Richardson, 1993;Dubový, Tučková, Jančálek, Svíženská, & Klusáková, 2007;Vega-Avelaira, Geranton, & Fitzgerald, 2009;Jager et al, 2020;Iwai et al, 2021). At present, however, this remains speculation until more functional data can be obtained.…”

Section: Discussionmentioning

confidence: 93%

Comparative transcriptional analysis of the satellite glial cell injury response

Jager

Pallesen

Lin

et al. 2021

Preprint

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Satellite glial cells (SGCs) tightly surround and support primary sensory neurons in the peripheral nervous system and are increasingly recognized for their involvement in the development of neuropathic pain following nerve injury. The SGCs are difficult to investigate due to their flattened shape and tight physical connection to neurons in vivo and their rapid changes in phenotype and protein expression when cultured in vitro. Consequently, several aspects of SGC function under normal conditions as well as after a nerve injury remain to be explored. The recent advance in single cell RNAseq technologies has enabled a new approach to investigate SGCs. Here we publish a dataset from mice subjected to sciatic nerve injury as well as a dataset from dorsal root ganglia cells after 3 days in culture. We use a meta-analysis approach to compare the injury response with that in other published datasets and conclude that SGCs share a common signature following sciatic nerve crush and sciatic ligation, involving transcriptional regulation of cholesterol biosynthesis. We also observed a considerable transcriptional change when culturing SGCs, suggesting that some differentiate into a specialised in vitro state, while others start resembling Schwann cell-like precursors. The datasets are available via the Broad Institute Single Cell Portal.

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“…As reported previously, polarized macrophages in the sensory ganglion can be detected by CD86 (marks M1 phenotype) and CD163 (marks M2 phenotype). 28 , 29 …”

Section: Resultsmentioning

confidence: 99%

Sympathectomy Ameliorates CFA-Induced Mechanical Allodynia via Modulating Phenotype of Macrophages in Sensory Ganglion in Mice

Mai¹,

Jia²,

Liu³

et al. 2022

JIR

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Background The sympathetic nervous system (SNS) is suggested to be involved in some forms of pain, but the mechanisms of which are incompletely known. Moreover, there is a lack of information on the regulatory role of the SNS on macrophages in sensory ganglion, which plays an important role in pain development. The present study aims to investigate the effects of the SNS on orofacial inflammatory pain and examine, if any, how the SNS influences trigeminal ganglion (TG) macrophage responses. Methods Sympathectomy was performed on male C57BL/6 mice before receiving a local injection of Complete Freund’s adjuvant (CFA) to induce inflammatory pain. Effects of sympathectomy on orofacial pain were examined by Von Frey test and c-Fos expression. Polarization of TG macrophage was evaluated by immunohistochemistry and the level of norepinephrine (NE) in the TG were determined by liquid chromatography. Sympathetic signaling to TG macrophages were predicted based on single-cell analysis. Results CFA injection induced a significant increase in mechanical allodynia, the number of c-Fos-positive neuron, and the level of NE in TG, which were largely reduced by sympathectomy. The number of M1 macrophages was markedly increased by CFA and was largely reduced by sympathectomy from 1 to 14 days post-injection. Single-cell RNA sequencing analysis and immunofluorescence staining showed that TG macrophages mainly express β2 adrenergic receptors for NE. Cell–cell communication analysis predicted sympathetic signaling that may modulate macrophage phenotypes, including Colony-stimulating factor-1, Migration inhibitory factor, Pleiotrophin and Nicotinamide phosphoribosyl transferase. Conclusion The SNS may involve in CFA-induced mechanical allodynia via modulating macrophage phenotypes in the TG. Targeting sympathetic activation might be useful in treating some painful conditions in the orofacial region.

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Tissue-resident M2 macrophages directly contact primary sensory neurons in the sensory ganglia after nerve injury

Cited by 31 publications

References 51 publications

Comparative transcriptional analysis of satellite glial cell injury response

Comparative transcriptional analysis of satellite glial cell injury response

Comparative transcriptional analysis of the satellite glial cell injury response

Sympathectomy Ameliorates CFA-Induced Mechanical Allodynia via Modulating Phenotype of Macrophages in Sensory Ganglion in Mice

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