{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:27:35Z","timestamp":1790116055462,"version":"4.0.1"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development, and Innovation","award":["451-03-33\/2026-03\/200161"],"award-info":[{"award-number":["451-03-33\/2026-03\/200161"]}]},{"name":"Ministry of Science, Technological Development, and Innovation","award":["451-03-34\/2026-03\/200161"],"award-info":[{"award-number":["451-03-34\/2026-03\/200161"]}]},{"award":["451-03-33\/2026-03\/200161"],"award-info":[{"award-number":["451-03-33\/2026-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]},{"award":["451-03-34\/2026-03\/200161"],"award-info":[{"award-number":["451-03-34\/2026-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Per- and polyfluoroalkyl substances (PFAS) are persistent, chemically stable compounds widely used in daily life. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were identified as the most relevant PFAS due to their prevalence and toxicity. This study aimed to investigate the immunotoxic mechanisms of a mixture of these PFAS using an in silico approach. Comparative Toxicogenomic Database (CTD), GeneMANIA, CytoHubba (Cytoscape), ToppGene Suite, and Metascape were used for the analysis. A total of 65 immune-related genes were identified as common to all four PFAS, with IFNG, TNF, IL1B, IL6, TYK2, CD3E, CASP8, VAV1, ARHGAP4, and CARD11 emerging as key hub genes. CTD phenotype analysis indicated immune dysregulation, with decreased humoral and adaptive immune responses in humans and tissue-specific modulation of B- and T-cell activity in mice, while no immune-related phenotypes were observed for PFNA. Network analysis identified functional modules associated with apoptotic and immune signaling, endothelial cell migration and angiogenesis, and shared inflammatory and viral response pathways. Disease enrichment analysis associated PFAS with autoimmune disorders (rheumatoid arthritis, asthma), metabolic conditions, and cardiovascular diseases (experimental diabetes, hypertensive disease). These results highlight PFAS involvement in immune modulation, cytokine signaling, and disease susceptibility.<\/jats:p>","DOI":"10.3390\/jox16030115","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Network Toxicology Framework for Identification of Immune System Disruption by Per- and Polyfluoroalkyl Substance (PFAS) Mixture: In Silico Analysis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3290-2204","authenticated-orcid":false,"given":"Katarina","family":"Barali\u0107","sequence":"first","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Vidi\u0107","sequence":"additional","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0110ur\u0111ica","family":"Mari\u0107","sequence":"additional","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovana","family":"\u017divanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6942-7040","authenticated-orcid":false,"given":"Aleksandra","family":"Buha Djordjevic","sequence":"additional","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4028-3108","authenticated-orcid":false,"given":"Marijana","family":"\u0106ur\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9830-8772","authenticated-orcid":false,"given":"Zorica","family":"Bulat","sequence":"additional","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-454X","authenticated-orcid":false,"given":"Biljana","family":"Antonijevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-9154","authenticated-orcid":false,"given":"Danijela","family":"\u0110uki\u0107-\u0106osi\u0107","sequence":"additional","affiliation":[{"name":"Department of Toxicology \u201cAkademik Danilo Soldatovi\u0107\u201d, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","first-page":"300","article-title":"Key Functions and Impact of the Immune System in Protecting and Disease Protection","volume":"21","author":"Singh","year":"2025","journal-title":"Immunome Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.taap.2005.01.025","article-title":"Low Level Exposure to Chemicals and Immune System","volume":"207","author":"Colosio","year":"2005","journal-title":"Toxicol. 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