Regulation of interleukin-12/interleukin-23 production and the T-helper 17 response in humans.

Abstract

Interleukin-12 (IL-12) and IL-23 share a common chain. Yet, their production in response to pathogens is differentially regulated, and their functions are distinct and often antithetic. IL-12 is involved in the induction or amplification of the T-helper (Th) type 1 response, whereas IL-23 has been associated with the generation of the Th17 response and IL-17 production. Mycobacterium tuberculosis and yeast zymosan induce IL-23, but in the absence of other stimuli, no IL-12 is induced in human dendritic cells (DCs). The stimulation of IL-23 by M. tuberculosis was mostly explained by the triggering of Toll-like receptor (TLR2) and the cytoplasmic receptor nucleotide oligomerization domain (NOD)-containing protein 2, whereas zymosan induces IL-23 primarily by stimulating the beta-glucan receptor dectin-1 alone or in combination with TLR2. IL-23, IL-6, transforming growth factor (TGF-beta1), and IL-1beta in supernatants from activated human DCs induce human naive CD4(+) T cells to produce IL-17. These data are consistent with various recent reports that TGF-beta is an inducer of IL-17 production both in human and in mouse cells. However, IL-1 is necessary in combination with some or all of the other cytokines to induce IL-17 production in human T cells. The ability of various stimuli to induce Th17 cells depends not only on their induction of IL-23, IL-6, and TGF-beta production in DCs but also on their ability to activate directly or indirectly the inflammasome and to induce IL-1beta.

• Authors: Lyudmila Lyakh, Giorgio Trinchieri, Lisa Provezza, Giuseppe Carra, Franca Gerosa
• Journal: Immunological reviews (Immunol Rev) Vol. 226 Pg. 112-31 (Dec 2008) ISSN: 1600-065X [Electronic] England
• PMID: 19161420 (Publication Type: Journal Article, Review)

Chemical References

• Interleukin-17
• Interleukin-23
• Toll-Like Receptors
• Transforming Growth Factor beta
• Interleukin-12
• Zymosan

Topics

• Cell Differentiation
• Dendritic Cells (immunology)
• Gene Expression Regulation (genetics, immunology)
• Humans
• Interleukin-12 (biosynthesis)
• Interleukin-17 (immunology)
• Interleukin-23 (biosynthesis)
• Mycobacterium tuberculosis (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Toll-Like Receptors (immunology)
• Transforming Growth Factor beta (immunology, metabolism)
• Zymosan (immunology)