Dataset Information

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities.

ABSTRACT: The interleukin 23 (IL-23) is a key pro-inflammatory cytokine in the development of chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases, multiple sclerosis, or rheumatoid arthritis. The pathological consequences of excessive IL-23 signaling have been linked to its ability to promote the production of inflammatory mediators, such as IL-17, IL-22, granulocyte-macrophage colony-stimulating (GM-CSF), or the tumor necrosis factor (TNF?) by target populations, mainly Th17 and IL-17-secreting TCR?? cells (T??17). Due to their pivotal role in inflammatory diseases, IL-23 and its downstream effector molecules have emerged as attractive therapeutic targets, leading to the development of neutralizing antibodies against IL-23 and IL-17 that have shown efficacy in different inflammatory diseases. Despite the success of monoclonal antibodies, there are patients that show no response or partial response to these treatments. Thus, effective therapies for inflammatory diseases may require the combination of multiple immune-modulatory drugs to prevent disease progression and to improve quality of life. Alternative strategies aimed at inhibiting intracellular signaling cascades using small molecule inhibitors or interfering peptides have not been fully exploited in the context of IL-23-mediated diseases. In this review, we discuss the current knowledge about proximal signaling events triggered by IL-23 upon binding to its membrane receptor to bring to the spotlight new opportunities for therapeutic intervention in IL-23-mediated pathologies.

SUBMITTER: Pastor-Fernandez G

PROVIDER: S-EPMC7563346 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities.

Pastor-Fernández Gloria G Mariblanca Isabel R IR Navarro María N MN

Cells 20200907 9

The interleukin 23 (IL-23) is a key pro-inflammatory cytokine in the development of chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases, multiple sclerosis, or rheumatoid arthritis. The pathological consequences of excessive IL-23 signaling have been linked to its ability to promote the production of inflammatory mediators, such as IL-17, IL-22, granulocyte-macrophage colony-stimulating (GM-CSF), or the tumor necrosis factor (TNFα) by target populations, mainly Th17 and ...[more]

PMID: 32906785

Similar Datasets

Project description:Uncontrolled activation of the Hedgehog/Glioma-associated oncogene (HH/GLI) pathway is a potent oncogenic driver signal promoting numerous cancer hallmarks such as proliferation, survival, angiogenesis, metastasis and metabolic rewiring. Several HH pathway inhibitors have already been approved for medical therapy of advanced and metastatic basal cell carcinoma and acute myeloid leukemia with partially impressive therapeutic activity. However, de novo and acquired resistance as well as severe side effects and unexplained lack of therapeutic efficacy are major challenges that urgently call for improved treatment options with more durable responses. The recent breakthroughs in cancer immunotherapy have changed our current understanding of targeted therapy and opened up promising therapeutic opportunities including combinations of selective cancer pathway and immune checkpoint inhibitors. Although HH/GLI signaling has been intensely studied with respect to the classical hallmarks of cancer, its role in the modulation of the anti-tumoral immune response has only become evident in recent studies. These have uncovered HH/GLI regulated immunosuppressive mechanisms such as enhanced regulatory T-cell formation and production of immunosuppressive cytokines. In light of these exciting novel data on oncogenic HH/GLI signaling in immune cross-talk and modulation, we summarize and connect in this review the existing knowledge from different HH-related cancers and chronic inflammatory diseases. This is to provide a basis for the investigation and evaluation of novel treatments combining immunotherapeutic strategies with approved as well as next-generation HH/GLI inhibitors. Further, we also critically discuss recent studies demonstrating a possible negative impact of current HH/GLI pathway inhibitors on the anti-tumoral immune response, which may explain some of the disappointing results of several oncological trials with anti-HH drugs. Additional file 1Video abstract. (9500 kb).

Dataset Information

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities.

Publications

Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure