| First Author | Colantuoni M | Year | 2023 |
| Journal | Sci Transl Med | Volume | 15 |
| Issue | 698 | Pages | eade3856 |
| PubMed ID | 37256935 | Mgi Jnum | J:336372 |
| Mgi Id | MGI:7488331 | Doi | 10.1126/scitranslmed.ade3856 |
| Citation | Colantuoni M, et al. (2023) Constitutive IL-1RA production by modified immune cells protects against IL-1-mediated inflammatory disorders. Sci Transl Med 15(698):eade3856 |
| abstractText | Dysregulation of the interleukin-1 (IL-1) pathway leads to immune diseases that can result in chronic tissue and organ inflammation. Although IL-1 blockade has shown promise in ameliorating these symptoms and improving patients' quality of life, there is an urgent need for more effective, long-lasting treatments. We developed a lentivirus (LV)-mediated gene transfer strategy using transplanted autologous hematopoietic stem/progenitor cells (HSPCs) as a source of IL-1 receptor antagonist (IL-1RA) for systemic delivery to tissues and organs. Transplantation of mouse and human HSPCs transduced with an IL-1RA-encoding LV ensured stable IL-1RA production while maintaining the clonogenic and differentiation capacities of HSPCs in vivo. We examined the efficacy of cell-mediated IL-1RA delivery in three models of IL-1-dependent inflammation, for which treatment hindered neutrophil recruitment in an inducible model of gout, prevented systemic and multi-tissue inflammation in a genetic model of cryopyrin-associated periodic syndromes, and reduced disease severity in an experimental autoimmune encephalomyelitis model of multiple sclerosis. Our findings demonstrate HSPC-mediated IL-1RA delivery as a potential therapeutic modality that can be exploited to suppress tissue and organ inflammation in diverse immune-related diseases involving IL-1-driven inflammation. |
