Details

Autor(en) / Beteiligte

• O'Sullivan, Brendan J
• Thomas, Helen E
• Pai, Saparna
• Santamaria, Pere
• Iwakura, Yoichiro
• Steptoe, Raymond J
• Kay, Thomas W H
• Thomas, Ranjeny

Titel

IL-1 beta breaks tolerance through expansion of CD25+ effector T cells

Ist Teil von

• The Journal of immunology (1950), 2006-06, Vol.176 (12), p.7278-7287

Ort / Verlag

United States

Erscheinungsjahr

2006

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.