{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:37Z","timestamp":1787027497004,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Moroccan Ministery of Higher Education, research, and Innovation","award":["2019 Call"],"award-info":[{"award-number":["2019 Call"]}]},{"name":"Moroccan Ministry of Higher Education, Research and Innovation","award":["PPR1"],"award-info":[{"award-number":["PPR1"]}]},{"name":"Moroccan Ministry of Higher Education, Research and Innovation","award":["Al-Khawarizmi"],"award-info":[{"award-number":["Al-Khawarizmi"]}]},{"DOI":"10.13039\/501100000780","name":"EUROPEAN COMMISSIONS","doi-asserted-by":"crossref","award":["624289-PANAF-1-2020-1-KEPANAFMOBAF"],"award-info":[{"award-number":["624289-PANAF-1-2020-1-KEPANAFMOBAF"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["624289-PANAF-1-2020-1-KEPANAFMOBAF"],"award-info":[{"award-number":["624289-PANAF-1-2020-1-KEPANAFMOBAF"]}],"id":[{"id":"https:\/\/ror.org\/00k4n6c32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Chronic inflammation in the tumor microenvironment (TME) promotes immune evasion and metastasis in breast cancer, where the IL-23\/IL-17 axis is a key mediator. We investigated the expression of IL-23 in breast cancer and identified a small natural molecule therapeutically targeting this axis. Methods: IL-23 expression and its clinicopathological significance were assessed in a Moroccan breast cancer cohort and the METABRIC dataset. A High-throughput virtual screening of Allium sativum L. compounds was conducted to target the IL-23\/IL-17 axis. In vitro, the selected candidate, IL-23RI, was evaluated for its effects on IL-17A and IFN\u03b3 production in human PBMCs using flow cytometry, as well as on the migration of MCF-7 and MDA-MB-231 breast cancer cells using wound-healing assays. Results: IL-23 was found to be overexpressed in aggressive breast cancer subtypes and correlated with unfavorable clinicopathological features and a poor prognosis. Elevated IL-23 expression was associated with an immunosuppressive TME, characterized by increased inhibitory immune checkpoints and immunosuppressive chemokines. In silico, IL-23RI demonstrates a high binding affinity for the IL-23 receptor, with a docking score of \u22127.482 kcal\/mol and a binding free energy of \u221248.80 kcal\/mol, stabilized by five hydrogen bonds. In vitro, IL-23RI selectively suppressed IL-17A production by CD4+ T cells without affecting IFN\u03b3 secretion by both CD4+ and CD8+ T cells. Furthermore, IL-23RI significantly inhibited the migration of MCF-7 and MDA-MB-231 breast cancer cells. Conclusions: These findings establish the IL-23\/IL-17 axis as a critical therapeutic target and present IL-23RI as a promising dual-function agent for breast cancer treatment, concurrently modulating immunity and inhibiting tumor cell migration.<\/jats:p>","DOI":"10.3390\/medsci14040485","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:00:05Z","timestamp":1786964405000},"page":"485","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Small Natural Molecule Targeting IL-23\/IL-17 Axis Exerts Dual Effects on T-Cell Function and Breast Cancer Cell Migration"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0934-8925","authenticated-orcid":false,"given":"Sara","family":"Bourdoukh","sequence":"first","affiliation":[{"name":"Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"El Azhary","sequence":"additional","affiliation":[{"name":"Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaa","family":"Souat","sequence":"additional","affiliation":[{"name":"Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-8597","authenticated-orcid":false,"given":"Khouloud","family":"Ayed","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza","family":"Benthami","sequence":"additional","affiliation":[{"name":"Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Byadi","sequence":"additional","affiliation":[{"name":"Organic Synthesis, Extraction and Valorization Laboratory, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0459-6935","authenticated-orcid":false,"given":"Aziz","family":"Aboulmouhajir","sequence":"additional","affiliation":[{"name":"Organic Synthesis, Extraction and Valorization Laboratory, Faculty of Sciences Ain Chock, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Elkarroumi","sequence":"additional","affiliation":[{"name":"Mohamed VI Oncology Center, Ibn Rochd University Hospital Center, Casablanca 20000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8507-0451","authenticated-orcid":false,"given":"Asma","family":"Gati","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics Immunology and Human Pathology, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4849-9085","authenticated-orcid":false,"given":"Abdallah","family":"Badou","sequence":"additional","affiliation":[{"name":"Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, Casablanca 20360, Morocco"},{"name":"City of Innovation and Technology Transfer, Hassan II University of Casablanca, Casablanca 20360, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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