biostudies-literatureSingh SKNIH Office of the Director and MD Anderson Cancer Center Core Grant NIHNIH Office of the DirectorNCI NIH HHSNINDS NIH HHSNIH HHSe154194https://www.ebi.ac.uk/biostudies/studies/S-EPMC8983134biostudies-literatureUnknown7(5)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 macropJCI insightCD8+ T cell-derived IL-13 increases macrophage IL-10 to resolve neuropathic pain.PMC8983134R21 NS104804P30 CA016672P51 OD011132R01 CA227064R01 CA208371R01 NS116704R01 NS073939NIH RO1 NS116704 (NINDS),NIH RO1 NS073939 (NINDS),NIH RO1 CA208371 (NCI),NIH RO1 CA227064 (NCI),NIH RO1 NS116704 (NINDS),NIH RO1 NS073939 (NINDS),NIH RO1 CA208371 (NCI),NIH RO1 CA227064 (NCI),NIH R21 NS104804 (NINDS),MD Anderson Cancer Center Core Grant NIH P30CA016672NIH R21 NS104804 (NINDS)Heijnen CJKavelaars AKrukowski KWeis DLaumet GOAlexander JFSingh SKfalseCD8+ T cell-derived IL-13 increases macrophage IL-10 to resolve neuropathic pain.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 macrop2022-01-01T00:00:00Z2022 Mar2025-04-19T21:48:14.63Z2025-04-19T21:48:14.63ZS-EPMC89831343526053510.1172/jci.insight.154194