Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27.
The interleukin (IL)-12 family, which is composed of heterodimeric cytokines including IL-12, IL-23, and IL-27, is produced by antigen-presenting cells such as macrophages and dendritic cells and plays critical roles in the regulation of helper T (Th) cell differentiation. IL-12 induces IFN-γ production by NK and T cells and differentiation to Th1 cells. IL-23 induces IL-17 production by memory T cells and expands and maintains inflammatory Th17 cells. IL-27 induces the early Th1 differentiation and generation of IL-10-producing regulatory T cells. In addition, these cytokines induce distinct immune responses to tumors. IL-12 activates signal transducers and activator of transcription (STAT)4 and enhances antitumor cellular immunity through interferon (IFN)-γ production. IL-27 activates STAT1, as does IFN-γ and STAT3 as well, and enhances antitumor immunity by augmenting cellular and humoral immunities. In contrast, although exogenously overexpressed IL-23 enhances antitumor immunity via memory T cells, endogenous IL-23 promotes protumor immunity through STAT3 activation by inducing inflammatory responses including IL-17 production.
Xu
Mingli
M
Intractable Disease Research Center, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
Mizoguchi
Izuru
I
Morishima
Noriko
N
Chiba
Yukino
Y
Mizuguchi
Junichiro
J
Yoshimoto
Takayuki
T
D000938:Antigen-Presenting Cells / Q000378:metabolism*; D002454:Cell Differentiation; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology
D020381:Interleukin-17; D053759:Interleukin-23; D018664:Interleukin-12