Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27.

Mingli Xu, Izuru Mizoguchi, Noriko Morishima, Yukino Chiba, Junichiro Mizuguchi, Takayuki Yoshimoto
Author Information
  1. Mingli Xu: Intractable Disease Research Center, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.

Abstract

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-�� 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)-�� production. IL-27 activates STAT1, as does IFN-�� 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.

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MeSH Term

Antigen-Presenting Cells
Cell Differentiation
Gene Expression Regulation
Humans
Interleukin-12
Interleukin-17
Interleukin-23
Neoplasms
T-Lymphocytes, Helper-Inducer

Chemicals

Interleukin-17
Interleukin-23
Interleukin-12

Word Cloud

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