title: 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.affiliation: Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Lyakh
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Lisa
authors.initials: L
authors.lastname: Provezza
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carra
authors.forename: Franca
authors.initials: F
authors.lastname: Gerosa
mesh_terms: D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000096:biosynthesis*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D015054:Zymosan / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D015054:Zymosan