ArticleProceedings of the National Academy of Sciences of the United States of America2021
Cytokine receptor clustering in sensory neurons with an engineered cytokine fusion protein triggers unique pain resolution pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
- Mas-Related G-Protein-Coupled Receptors: Emerging Roles in Neuropathic Pain.Biomolecules · 2026Review
- The Role of the CCR5 Receptor in Neuropathic Pain Modulation: Current Insights and Therapeutic Implications.Biomedicines · 2025Review
- Distinct Alterations of Inflammatory Biomarkers in Cluster Headache: A Case Control Study.Annals of neurology · 2025Article
- Upregulation of delta opioid receptor by meningeal interleukin-10 prevents relapsing pain.Brain, behavior, and immunity · 2025Article
- Immune drivers of pain resolution and protection.Nature immunology · 2024Review
- Review
- Interactions and Trends of Interleukins, PAI-1, CRP, and TNF-α in Inflammatory Responses during the Perioperative Period of Joint Arthroplasty: Implications for Pain Management-A Narrative Review.Journal of personalized medicine · 2024Review
- Interleukin-1α links peripheral CaScientific reports · 2024Article
- Mast cell-sensory neuron crosstalk in allergic diseases.The Journal of allergy and clinical immunology · 2024Review
- Interleukin-1α links peripheral CabioRxiv : the preprint server for biology · 2024Article
- Interleukin-10 signaling in somatosensory neurons controls CCL2 release and inflammatory response.Brain, behavior, and immunity · 2024Review
- Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain.Cell reports. Medicine · 2023Article
- Role of SIRT5 in the analgesic effectiveness of moxibustion at ST36 in mice with inflammatory pain.Heliyon · 2023Article
- Inducible co-stimulatory molecule (ICOS) alleviates paclitaxel-induced neuropathic pain via an IL-10-mediated mechanism in female mice.Journal of neuroinflammation · 2023Article
- Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs.Frontiers in immunology · 2023Review
- M2 macrophage polarization: a potential target in pain relief.Frontiers in immunology · 2023Review
- The Experience of BIPOC Living with Chronic Pain in the USA: Biopsychosocial Factors that Underlie Racial Disparities in Pain Outcomes, Comorbidities, Inequities, and Barriers to Treatment.Current pain and headache reports · 2023Review
- Sensitization of colonic nociceptors by TNFα is dependent on TNFR1 expression and p38 MAPK activity.The Journal of physiology · 2022Article
- An HDAC6 inhibitor reverses chemotherapy-induced mechanical hypersensitivity via an IL-10 and macrophage dependent pathway.Brain, behavior, and immunity · 2022Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New therapeutic approaches to resolve persistent pain are highly needed. We tested the hypothesis that manipulation of cytokine receptors on sensory neurons by clustering regulatory cytokine receptor pairs with a fusion protein of interleukin (IL)-4 and IL-10 (IL4-10 FP) would redirect signaling pathways to optimally boost pain-resolution pathways. We demonstrate that a population of mouse sensory neurons express both receptors for the regulatory cytokines IL-4 and IL-10. This population increases during persistent inflammatory pain. Triggering these receptors with IL4-10 FP has unheralded biological effects, because it resolves inflammatory pain in both male and female mice. Knockdown of both IL4 and IL10 receptors in sensory neurons in vivo ablated the IL4-10 FP-mediated inhibition of inflammatory pain. Knockdown of either one of the receptors prevented the analgesic gain-of-function of IL4-10 FP. In vitro, IL4-10 FP inhibited inflammatory mediator-induced neuronal sensitization more effectively than the combination of cytokines, confirming its superior activity. The IL4-10 FP, contrary to the combination of IL-4 and IL-10, promoted clustering of IL-4 and IL-10 receptors in sensory neurons, leading to unique signaling, that is exemplified by activation of shifts in the cellular kinome and transcriptome. Interrogation of the potentially involved signal pathways led us to identify JAK1 as a key downstream signaling element that mediates the superior analgesic effects of IL4-10 FP. Thus, IL4-10 FP constitutes an immune-biologic that clusters regulatory cytokine receptors in sensory neurons to transduce unique signaling pathways required for full resolution of persistent inflammatory pain.
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