CD8+ T cell-derived IL-13 increases macrophage IL-10 to resolve neuropathic pain.
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| Abstract |
Understanding the endogenous mechanisms regulating resolution of pain may identify novel targets for treatment of chronic pain. Resolution of chemotherapy-induced peripheral neuropathy (CIPN) after treatment completion depends on CD8+ T cells and on IL-10 produced by other cells. Using Rag2-/- mice lacking T and B cells and adoptive transfer of Il13-/- CD8+ T cells, we showed that CD8+ T cells producing IL-13 were required for resolution of CIPN. Intrathecal administration of anti-IL-13 delayed resolution of CIPN and reduced IL-10 production by dorsal root ganglion macrophages. Depleting local CD206+ macrophages also delayed resolution of CIPN. In vitro, TIM3+CD8+ T cells cultured with cisplatin, apoptotic cells, or phosphatidylserine liposomes produced IL-13, which induced IL-10 in macrophages. In vivo, resolution of CIPN was delayed by intrathecal administration of anti-TIM3. Resolution was also delayed in Rag2-/- mice reconstituted with Havcr2 (TIM3)-/- CD8+ T cells. Our data indicated that cell damage induced by cisplatin activated TIM3 on CD8+ T cells, leading to increased IL-13 production, which in turn induced macrophage IL-10 production and resolution of CIPN. Development of exogenous activators of the IL-13/IL-10 pain resolution pathway may provide a way to treat the underlying cause of chronic pain.
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| Authors | Susmita K Singh, Karen Krukowski, Geoffroy O Laumet, Drew Weis, Jenolyn F Alexander, Cobi J Heijnen, Annemieke Kavelaars |
| Journal | JCI insight (JCI Insight) Vol. 7 Issue 5 (03 08 2022) ISSN: 2379-3708 [Electronic] United States |
| PMID | 35260535 (Publication Type: Journal Article) |
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