CD8+ T cell–derived IL-13 increases macrophage IL-10 to resolve neuropathic pain

Singh, Som Nath; Krukowski, Karen; Laumet, Geoffroy; Weis, Drew; Alexander, Jenolyn F.; Heijnen, Cobi J.; Kavelaars, Annemieke

doi:10.1172/jci.insight.154194

Cited by 47 publications

(28 citation statements)

References 54 publications

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“…In addition, it can act as an analgesic by stimulating macrophages to produce the analgesic factor IL-10. 14 However, more in-depth studies on its analgesic properties are yet to be detected. Both IL-4 and IL-13 have analgesic effects, so we hypothesized that when dupilumab antagonized IL-4Rα and thus inhibited the IL-4, and IL-13 pathway, the skin showed pain sensitivity especially in the lesions that were improving because the barrier was being reconstructed.…”

Section: Discussionmentioning

confidence: 99%

Burning and Scaling Probably Associated with Dupilumab Therapy: A Case Report

Luo¹,

Wang²,

M³

et al. 2022

CCID

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Case Report We present the case of a 51-year-old male who experienced temporary desquamation and recurrent burning sensation in primary skin lesions after the injection of dupilumab. The scaling lasted for 1 week and subsided, while the burning became aggravated with each injection of dupilumab, which gradually subsides after 8 weeks, and there was no recurrence since then. Conclusion Dupilumab is an emerging and efficacious biologics medication for AD. The burning sensation and scaling we report may be the adverse events of dupilumab. Rare adverse reactions to biologics deserve the attention of physicians.

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Section: Discussionmentioning

confidence: 99%

Burning and Scaling Probably Associated with Dupilumab Therapy: A Case Report

Luo¹,

Wang²,

M³

et al. 2022

CCID

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“…However, another study using the same model showed that T cells likely play a more important role in promoting neuropathic pain in female mice than in male mice [55]. Since this time, it has become clear that the type of T cell is critical for understanding the impact of these cells on neuropathic pain and neuropathic pain resolution [52]. Another potential reason for this difference in the duration of effect is that the SNI model creates a situation where nociceptor spontaneous activity is continuously driven by the ligation injury to the injured nerves.…”

Section: Discussionmentioning

confidence: 99%

Inducible co-stimulatory molecule (ICOS) alleviates Paclitaxel induced peripheral neuropathy via an IL-10-mediated mechanism in female mice

Sankaranarayanan

Tavares‐Ferreira

Mwrigi

et al. 2022

Preprint

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Chemotherapy-induced peripheral neuropathy (CIPN) is a primary dose-limiting side effect caused by antineoplastic agents, such as paclitaxel. This causes damage to peripheral nerves and the dorsal root ganglia (DRG). Currently, there are no effective treatments for CIPN, which can lead to long-term morbidity in cancer patients and survivors. Neuro-immune interactions occur in CIPN and have been implicated both in the development and progression of the disease and disease resolution. We investigated the potential role of Inducible co-stimulatory molecule (ICOS) in the resolution of CIPN pain-like behaviors in mice. ICOS is an immune checkpoint molecule that is expressed on the surface of activated T cells and promotes proliferation and differentiation of T cells. We found that intrathecal administration of ICOS agonist antibody (ICOSaa) alleviates mechanical hypersensitivity caused by paclitaxel and facilitates the resolution of mechanical sensitivity in female mice. Administration of ICOSaa reduced astrocyte-gliosis in the spinal cord and satellite cell gliosis in the DRG of mice previously treated with paclitaxel. Mechanistically, ICOSaa intrathecal treatment promoted pain resolution by increasing interleukin 10 (IL-10) expression in the dorsal root ganglion. In line with these observations, blocking IL-10 receptor (IL-10R) activity occluded the effects of ICOSaa treatment on CIPN behavior in female mice. Suggesting a broader activity in neuropathic pain, ICOSaa also partially resolved mechanical hypersensitivity in the spared nerve injury (SNI) model. Our findings support a model wherein ICOSaa administration induces IL-10 expression to facilitate neuropathic pain relief in female mice. ICOSaa treatment is in clinical development for solid tumors and given our observation of T cells in the human DRG, ICOSaa therapy could be developed for combination chemotherapy - CIPN clinical trials.HighlightsICOS agonist antibody (ICOSaa) promotes pain resolution in female miceDRG T cells appear to enter an anti-inflammatory phenotype by ICOSaa treatmentICOSaa treatment increases DRG levels of IL-10 cytokineICOSaa effects in female mice are blocked by IL-10 sequestering treatment

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“…(Basso et al, 2015 ; Swain et al, 2022 ). Recent studies have found that T cells are also involved in neuropathic pain: CD8 + T cells and endogenous IL-10 are required to resolve chemotherapy-induced neuropathic pain (Krukowski et al, 2016 ); educating CD8 + T cells can prevent and resolve chemotherapy-induced peripheral neuropathy in mice (Laumet et al, 2019 ; Singh et al, 2022 ). Intriguingly, in the bone cancer pain model which may involve both inflammatory pain and neuropathic pain, systemic administration of STING activator DMXAA attenuated the measures of spontaneous and ongoing pain; the analgesic effect may attribute to the increasing proportion of CD8 + T cells in the bone marrow tumor microenvironment (Donnelly et al, 2021 ).…”

Section: The Potential Mechanism Of the Cgas-sting Pathway In Chronic...mentioning

confidence: 99%

What role of the cGAS-STING pathway plays in chronic pain?

Zhang

et al. 2022

Front. Mol. Neurosci.

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Chronic pain interferes with daily functioning and is frequently accompanied by depression. Currently, traditional clinic treatments do not produce satisfactory analgesic effects and frequently result in various adverse effects. Pathogen recognition receptors (PRRs) serve as innate cellular sensors of danger signals, sense invading microorganisms, and initiate innate and adaptive immune responses. Among them, cGAS-STING alerts on the presence of both exogenous and endogenous DNA in the cytoplasm, and this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection, and cancer. An increasing numbers of evidence suggest that cGAS-STING pathway involves in the chronic pain process; however, its role remains controversial. In this narrative review, we summarize the recent findings on the involvement of the cGAS-STING pathway in chronic pain, as well as several possible mechanisms underlying its activation. As a new area of research, this review is unique in considering the cGAS-STING pathway in sensory neurons and glial cells as a part of a broader understanding of pain, including potential mechanisms of inflammation, immunity, apoptosis, and autophagy. It will provide new insight into the treatment of pain in the future.

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CD8+ T cell–derived IL-13 increases macrophage IL-10 to resolve neuropathic pain

Cited by 47 publications

References 54 publications

Burning and Scaling Probably Associated with Dupilumab Therapy: A Case Report

Burning and Scaling Probably Associated with Dupilumab Therapy: A Case Report

Inducible co-stimulatory molecule (ICOS) alleviates Paclitaxel induced peripheral neuropathy via an IL-10-mediated mechanism in female mice

What role of the cGAS-STING pathway plays in chronic pain?

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