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Novel IL-12 family members shed light on the orchestration of Th1 responses
Frank Brombacher1, Robert A Kastelein, Gottfried Alber
1University of Cape Town, Division of Immunology, Groote Schuur Hospital, 7925 Cape Town, South Africa.
Abstract:
Interleukin-12 (IL-12), which is composed of a p35 and a p40 subunit, is a proinflammatory natural-killer (NK) cell-stimulating, Th1-inducing and Th1-maintaining cytokine, which promotes cell-mediated immunity. On activation, heterodimeric IL-12 is found in small amounts, whereas free p40 is produced in excess. Besides IL-12, other p40-dependent molecules exist that orchestrate Th1 responses. Homodimeric p40 can act as an IL-12 antagonist by competing for its receptor. Recent data also reveal potential immunostimulatory functions of p40. In addition, p40 can be covalently linked to a p35-related protein p19. This heterodimer is known as IL-23 and has activities on memory T cells. Finally, IL-27, the latest addition to this family, is a heterodimer composed of the p40-related protein EBI3 (Epstein-Barr virus-induced gene 3) and the p35-related protein p28. IL-27 is involved in early Th1 initiation.
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