| First Author | O'Sullivan BJ | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 12 | Pages | 7278-87 |
| PubMed ID | 16751371 | Mgi Jnum | J:132225 |
| Mgi Id | MGI:3775539 | Doi | 10.4049/jimmunol.176.12.7278 |
| Citation | O'Sullivan BJ, et al. (2006) IL-1 beta breaks tolerance through expansion of CD25+ effector T cells. J Immunol 176(12):7278-87 |
| abstractText | IL-1 is a key proinflammatory driver of several autoimmune diseases including juvenile inflammatory arthritis, diseases with mutations in the NALP/cryopyrin complex and Crohn's disease, and is genetically or clinically associated with many others. IL-1 is a pleiotropic proinflammatory cytokine; however the mechanisms by which increased IL-1 signaling promotes autoreactive T cell activity are not clear. Here we show that autoimmune-prone NOD and IL-1 receptor antagonist-deficient C57BL/6 mice both produce high levels of IL-1, which drives autoreactive effector cell expansion. IL-1beta drives proliferation and cytokine production by CD4(+)CD25(+)FoxP3(-) effector/memory T cells, attenuates CD4(+)CD25(+)FoxP3(+) regulatory T cell function, and allows escape of CD4(+)CD25(-) autoreactive effectors from suppression. Thus, inflammation or constitutive overexpression of IL-1beta in a genetically predisposed host can promote autoreactive effector T cell expansion and function, which attenuates the ability of regulatory T cells to maintain tolerance to self. |
