Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain

Oggero, Silvia; Cecconello, Chiara; Silva, Rita; Zeboudj, Lynda; Sideris-Lampretsas, George; Perretti, Mauro; Malcangio, Marzia

doi:10.1016/j.bbi.2022.09.008

Cited by 19 publications

(13 citation statements)

References 38 publications

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“…The detection of CD127 (IL-7Ra) further points to monocytes’ sensitivity to IL-7 signals, essential for their survival and operational integrity ( 46 ). Moreover, CX3CR1 and CXCR5 expressions imply their engagement in site-specific migration and homing, critical for targeted recruitment to inflamed and lymphoid tissues ( 47 , 48 ). Expression patterns of CD39 and CD73 indicate monocytes’ involvement in adenosine-dependent immune regulation, influencing inflammation resolution and tissue repair mechanisms ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of human monocyte subsets using full-spectrum flow cytometry and hierarchical marker clustering

Li,

Xiao,

Geng

et al. 2024

Front. Immunol.

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IntroductionExploring monocytes’ roles within the tumor microenvironment is crucial for crafting targeted cancer treatments.MethodsThis study unveils a novel methodology utilizing four 20-color flow cytometry panels for comprehensive peripheral immune system phenotyping, specifically targeting classical, intermediate, and non-classical monocyte subsets. ResultsBy applying advanced dimensionality reduction techniques like t-distributed stochastic neighbor embedding (tSNE) and FlowSom analysis, we performed an extensive profiling of monocytes, assessing 50 unique cell surface markers related to a wide range of immunological functions, including activation, differentiation, and immune checkpoint regulation. DiscussionThis in-depth approach significantly refines the identification of monocyte subsets, directly supporting the development of personalized immunotherapies and enhancing diagnostic precision. Our pioneering panel for monocyte phenotyping marks a substantial leap in understanding monocyte biology, with profound implications for the accuracy of disease diagnostics and the success of checkpoint-inhibitor therapies. Key findings include revealing distinct marker expression patterns linked to tumor progression and providing new avenues for targeted therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of human monocyte subsets using full-spectrum flow cytometry and hierarchical marker clustering

Li,

Xiao,

Geng

et al. 2024

Front. Immunol.

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“…Neuroimmune interactions are critical to the establishment of persistent painful states 10 , 15 , 80 . For example, experiments in mouse models of arthritis and vincristine-induced toxicity have shown that the infiltration of blood-derived CX3CR1-expressing monocytes into the DRG drives the induction and maintenance of persistent pathological nociception 15 , 16 . Similarly, after nerve injury in mice, blood-borne monocytes migrate to the spinal cord, where they proliferate, differentiate, and act in synergy with microglia to initiate pain chronification 12 – 14 .…”

Section: Discussionmentioning

confidence: 99%

“…Studies in mice have shown, for example, that blood-borne monocytes infiltrate the spinal cord 12 and act in synergy with local microglia to promote pain chronification after nerve injury 13 , 14 . Similarly, monocytes and macrophages that express the CX3CR1 receptor contribute to arthritis pain and chemotherapy-induced allodynia by interacting with nociceptive neurons in dorsal root ganglia (DRG) 15 , 16 . Despite these advances, the molecular checkpoints that trigger the deployment of monocyte-derived cells during the transition from acute to chronic pain are still poorly understood 8 – 10 .…”

Section: Introductionmentioning

confidence: 99%

NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice

Fotio,

Mabou Tagne,

Squire

et al. 2024

Nat Commun

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Circulating monocytes participate in pain chronification but the molecular events that cause their deployment are unclear. Using a mouse model of hyperalgesic priming (HP), we show that monocytes enable progression to pain chronicity through a mechanism that requires transient activation of the hydrolase, N-acylethanolamine acid amidase (NAAA), and the consequent suppression of NAAA-regulated lipid signaling at peroxisome proliferator-activated receptor-α (PPAR-α). Inhibiting NAAA in the 72 hours following administration of a priming stimulus prevented HP. This effect was phenocopied by NAAA deletion and depended on PPAR-α recruitment. Mice lacking NAAA in CD11b+ cells – monocytes, macrophages, and neutrophils – were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-α in the same cells were constitutively primed. Depletion of monocytes, but not resident macrophages, generated mice that were refractory to HP. The results identify NAAA-regulated signaling in monocytes as a control node in the induction of HP and, potentially, the transition to pain chronicity.

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“…Neuroimmune interactions are critical to the establishment of persistent painful states 10,15,76 . For example, experiments in mouse models of arthritis and vincristine-induced toxicity have shown that the infiltration of blood-derived CXCR1-expressing monocytes into the DRG drives initiation and maintenance of persistent pathological nociception 15,16 . Similarly, after nerve injury in mice, blood-borne monocytes migrate to the spinal cord, where they proliferate, differentiate, and act in synergy with microglia to initiate pain chronification [12][13][14] .…”

Section: Discussionmentioning

confidence: 99%

NAAA-regulated lipid signaling in monocyte-derived cells controls the induction of hyperalgesic priming

Piomelli,

Fotio,

Tagne

et al. 2023

Preprint

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Circulating monocytes and tissue-resident macrophages contribute in important ways to the transition from acute to chronic pain but the molecular events that cause their deployment are still unclear. Using a mouse model of hyperalgesic priming (HP), we show now that monocyte-derived cells enable the progression to pain chronicity through a cell-autonomous mechanism that requires the transient activation of the intracellular lipid hydrolase, N-acylethanolamine acid amidase (NAAA), and the consequent suppression of NAAA-regulated lipid signaling at peroxisome proliferator-activated receptor-α (PPAR-α). Inhibiting peripheral NAAA in the 72 hours following administration of one of three different priming stimuli (interleukin-6, tumor necrosis factor-α, or carrageenan), but not before or after this time interval, prevented the emergence of HP in male and female mice. This effect was phenocopied by global NAAA deletion and depended on the recruitment of PPAR-α by endogenous NAAA substrates. Transgenic mice selectively lacking NAAA in CD11b+ myeloid cells – which include monocytes, macrophages, and neutrophils – were resistant to HP induction. Conversely, mice overexpressing NAAA or lacking PPAR-α in the same cells were constitutively primed. In vivo ablation of monocytes, but not neutrophils, by administration of clodronate liposomes or blockade of type-1 colony-stimulating factor receptors, generated mice that were refractory to priming. The results identify NAAA-regulated lipid signaling in monocyte-derived cells as a control node in the induction of HP and the transition to pain chronicity.

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Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain

Cited by 19 publications

References 38 publications

Comprehensive analysis of human monocyte subsets using full-spectrum flow cytometry and hierarchical marker clustering

Comprehensive analysis of human monocyte subsets using full-spectrum flow cytometry and hierarchical marker clustering

NAAA-regulated lipid signaling in monocytes controls the induction of hyperalgesic priming in mice

NAAA-regulated lipid signaling in monocyte-derived cells controls the induction of hyperalgesic priming

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