| First Author | Mufazalov IA | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 4 | Pages | 747-751 |
| PubMed ID | 31924653 | Mgi Jnum | J:284032 |
| Mgi Id | MGI:6388978 | Doi | 10.4049/jimmunol.1900876 |
| Citation | Mufazalov IA, et al. (2020) Cutting Edge: IL-6-Driven Immune Dysregulation Is Strictly Dependent on IL-6R alpha-Chain Expression. J Immunol 204(4):747-751 |
| abstractText | IL-6 binds to the IL-6R alpha-chain (IL-6Ralpha) and signals via the signal transducer gp130. Recently, IL-6 was found to also bind to the cell surface glycoprotein CD5, which would then engage gp130 in the absence of IL-6Ralpha. However, the biological relevance of this alternative pathway is under debate. In this study, we developed a mouse model, in which murine IL-6 is overexpressed in a CD11c-Cre-dependent manner. Transgenic mice developed a lethal immune dysregulation syndrome with increased numbers of Ly-6G(+) neutrophils and Ly-6C(hi) monocytes/macrophages. IL-6 overexpression promoted activation of CD4(+) T cells while suppressing CD5(+) B-1a cell development. However, additional ablation of IL-6Ralpha protected IL-6-overexpressing mice from IL-6-triggered inflammation and fully phenocopied IL-6Ralpha-deficient mice without IL-6 overexpression. Mechanistically, IL-6Ralpha deficiency completely prevented downstream activation of STAT3 in response to IL-6. Altogether, our data clarify that IL-6Ralpha is the only biologically relevant receptor for IL-6 in mice. |
