Decoding IL-23 Signaling Cascade for New Therapeutic Opportunities
| Autor: | Isabel R. Mariblanca, Gloria Pastor-Fernández, María N. Navarro |
|---|---|
| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación Ramón Areces, Banco Santander |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
medicine.medical_treatment Context (language use) Autoimmunity Review Monoclonal antibody medicine.disease_cause Interleukin-23 Multiple sclerosis IL-23 Interleukin 17 Interleukin 23 medicine Humans Psoriasis lcsh:QH301-705.5 business.industry Effector General Medicine Signaling Inflammatory disease Cytokine lcsh:Biology (General) Immunology Tumor necrosis factor alpha business Signal Transduction |
| Zdroj: | Cells Digital.CSIC. Repositorio Institucional del CSIC instname Cells, Vol 9, Iss 2044, p 2044 (2020) |
| Popis: | © 2020 by the authors. 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 IL-17-secreting TCRγδ cells (Tγδ17). 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. This work was supported by grants from the Spanish Ministry of Economy and Competitiveness and Spanish Ministry of Science and Innovation. M.N.N., G.P.-F. and I.R.M. are funded by grants SAF2013-43833-R, SAF2016-78180-R and PID2019-110511RB-I00 to M.N.N. Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged. |
| Databáze: | OpenAIRE |
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