Dataset Information

Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages.

ABSTRACT: The development of effective treatments against cancers is urgently needed, and the accumulation of CD8+ T cells within tumors is especially important for cancer prognosis. Although their mechanisms are still largely unknown, growing evidence has indicated that innate immune cells have important effects on cancer progression through the production of various cytokines. Here, we found that basic leucine zipper transcription factor ATF-like 2 (Batf2) has an antitumor effect. An s.c. inoculated tumor model produced fewer IL-12 p40+ macrophages and activated CD8+ T cells within the tumors of Batf2-/- mice compared with WT mice. In vitro studies also revealed that the IL-12 p40 expression was significantly lower in Batf2-/- macrophages following their stimulation by toll-like receptor ligands, such as R848. Additionally, we found that BATF2 interacts with p50/p65 and promotes IL-12 p40 expression. In conclusion, Batf2 has an antitumor effect through the up-regulation of IL-12 p40 in tumor-associated macrophages, which eventually induces CD8+ T-cell activation and accumulation within the tumor.

SUBMITTER: Kanemaru H

PROVIDER: S-EPMC5584452 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages.

Kanemaru Hisashi H Yamane Fumihiro F Fukushima Kiyoharu K Matsuki Takanori T Kawasaki Takahiro T Ebina Isao I Kuniyoshi Kanako K Tanaka Hiroki H Maruyama Kenta K Maeda Kazuhiko K Satoh Takashi T Akira Shizuo S

Proceedings of the National Academy of Sciences of the United States of America 20170814 35

The development of effective treatments against cancers is urgently needed, and the accumulation of CD8+ T cells within tumors is especially important for cancer prognosis. Although their mechanisms are still largely unknown, growing evidence has indicated that innate immune cells have important effects on cancer progression through the production of various cytokines. Here, we found that basic leucine zipper transcription factor ATF-like 2 (Batf2) has an antitumor effec ...[more]

PMID: 28808017

Similar Datasets

Project description:Porphyromonas gingivalis (P. gingivalis) is a major periodontal pathogen that can induce an immune response leading to a destructive inflammatory process. During the inflammatory process, interleukin-12 (IL-12) is secreted, correlating with bacterial clearance by macrophages. Bacterial sialidase has recently been shown to influence the synthesis and modification of the macromolecules on its surface, and is associated with the interaction between bacteria and host cells. We have previously constructed a P. gingivalis sialidase gene mutant strain in P. gingivalis W83 (ΔPG0352) and found that ΔPG0352 showed less pathogenicity than the wild-type strain. In this study, U937-differentiated macrophages were stimulated by P. gingivalis W83, ΔPG0352, or PG0352 complemented strain (comΔPG0352). Transmission electron microscopy showed that P. gingivalis caused a loss of membrane integrity in macrophages and the intracellular bacteria were enclosed within endocytic vacuoles. The expression of both IL-12p35 and IL-12p40 genes and the levels of IL-12p70 were significantly higher in U937 stimulated by ΔPG0352 than in those with P. gingivalis W83 and comΔPG0352. In order to explain why ΔPG0352 induced more IL-12 in macrophages, immunofluorescence assays, PCR arrays, and gene silence or overexpression experiments were carried out. Immunofluorescence assays showed that ΔPG0352 induced lower expression of CR3 in macrophages. After CR3 was suppressed, there were no significant differences in the IL-12p70 levels between macrophages stimulated by P. gingivalis W83, ΔPG0352 or comΔPG0352. PCR array experiments showed that miR-21 and lncRNA GAS5 were differentially expressed between macrophages stimulated by P. gingivalis W83 and ΔPG0352, which had been identified by real-time PCR. The results of CR3 blocking and lncRNA GAS5 gene silence or overexpression showed that the difference in IL-12 levels between P. gingivalis W83 and ΔPG0352 groups was associated with CR3, lncRNA GAS5 and miR-21. Thus it can be concluded that the sialidase-deficient strain is more easily cleared by attenuating CR3 activation, reducing the inhibition of lncRNA GAS5, inducing less miR-21 and more IL-12 in macrophages. These results indicate that inhibiting the activity of sialidase in P. gingivalis will cause rapid clearing by macrophages.

Dataset Information

Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages.

Publications

Antitumor effect of <i>Batf2</i> through IL-12 p40 up-regulation in tumor-associated macrophages.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets