Novel IL-12 family members shed light on the orchestration of Th1 responses.
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.
Brombacher
Frank
F
University of Cape Town, Division of Immunology, Groote Schuur Hospital, 7925 Cape Town, South Africa.
Kastelein
Robert A
RA
Alber
Gottfried
G
D000818:Animals; D003141:Communicable Diseases / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*
C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; C464565:MYDGF protein, human; D018664:Interleukin-12