A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism
<p dir="ltr">Peripheral immune dysregulation is frequently reported in autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. We recruited a well-defined cohort of young Arab children with ASD, aged 2–4 years, along with matched controls in Qatar...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2025
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| _version_ | 1864513525561425920 |
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| author | Wared Nour-Eldine (13904298) |
| author2 | Samia M. Ltaief (11405336) Khalid Ouararhni (3145734) Nimshitha P. Abdul Manaph (18420834) Alberto de la Fuente (360936) Ilham Bensmail (12204845) Houari B. Abdesselem (14152827) Abeer R. Al-Shammari (11405339) |
| author2_role | author author author author author author author |
| author_facet | Wared Nour-Eldine (13904298) Samia M. Ltaief (11405336) Khalid Ouararhni (3145734) Nimshitha P. Abdul Manaph (18420834) Alberto de la Fuente (360936) Ilham Bensmail (12204845) Houari B. Abdesselem (14152827) Abeer R. Al-Shammari (11405339) |
| author_role | author |
| dc.creator.none.fl_str_mv | Wared Nour-Eldine (13904298) Samia M. Ltaief (11405336) Khalid Ouararhni (3145734) Nimshitha P. Abdul Manaph (18420834) Alberto de la Fuente (360936) Ilham Bensmail (12204845) Houari B. Abdesselem (14152827) Abeer R. Al-Shammari (11405339) |
| dc.date.none.fl_str_mv | 2025-07-30T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41435-025-00349-z |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/A_multi-omics_approach_reveals_dysregulated_TNF-related_signaling_pathways_in_circulating_NK_and_T_cell_subsets_of_young_children_with_autism/30971347 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Immunology Neurosciences Autism Spectrum Disorder (ASD) Peripheral immune dysregulation Transcriptomics Proteomics Neuroimmunology |
| dc.title.none.fl_str_mv | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Peripheral immune dysregulation is frequently reported in autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. We recruited a well-defined cohort of young Arab children with ASD, aged 2–4 years, along with matched controls in Qatar. Using a multimodal approach, we integrated transcriptomic, proteomic, and single-cell RNA-seq data analyses from this cohort. Targeted transcriptomic profiling identified differential expression of 50 immune-related genes in the circulating PBMCs of children with ASD, three of which (JAK3, CUL2, and CARD11) negatively correlated with ASD symptom severity. These gene signatures were validated in independent studies using blood and brain tissues from individuals with ASD. Enrichment analysis revealed involvement of these genes in immune function, particularly through TNF signaling pathway. Proteomic analysis highlighted disrupted TNF signaling and upregulated levels of TNFSF10 (TRAIL), TNFSF11 (RANKL), and TNFSF12 (TWEAK) in plasma of individuals with ASD. Single-cell RNA-seq revealed that B cells, CD4 T cells, and NK cells potentially contributed to these upregulations in ASD. Dysregulated TRAIL, RANKL, and TWEAK signaling pathways were specifically observed in CD8 T cells, CD4 T cells, and NK cells of individuals with ASD. These findings provide new insights into immune dysregulation mechanisms in ASD and highlight potential therapeutic targets.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Genes & Immunity<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41435-025-00349-z" target="_blank">https://dx.doi.org/10.1038/s41435-025-00349-z</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d55d798ff005678023b47437088c35a4 |
| identifier_str_mv | 10.1038/s41435-025-00349-z |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/30971347 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autismWared Nour-Eldine (13904298)Samia M. Ltaief (11405336)Khalid Ouararhni (3145734)Nimshitha P. Abdul Manaph (18420834)Alberto de la Fuente (360936)Ilham Bensmail (12204845)Houari B. Abdesselem (14152827)Abeer R. Al-Shammari (11405339)Biological sciencesGeneticsBiomedical and clinical sciencesImmunologyNeurosciencesAutism Spectrum Disorder (ASD)Peripheral immune dysregulationTranscriptomicsProteomicsNeuroimmunology<p dir="ltr">Peripheral immune dysregulation is frequently reported in autism spectrum disorder (ASD); however, the underlying molecular mechanisms remain unclear. We recruited a well-defined cohort of young Arab children with ASD, aged 2–4 years, along with matched controls in Qatar. Using a multimodal approach, we integrated transcriptomic, proteomic, and single-cell RNA-seq data analyses from this cohort. Targeted transcriptomic profiling identified differential expression of 50 immune-related genes in the circulating PBMCs of children with ASD, three of which (JAK3, CUL2, and CARD11) negatively correlated with ASD symptom severity. These gene signatures were validated in independent studies using blood and brain tissues from individuals with ASD. Enrichment analysis revealed involvement of these genes in immune function, particularly through TNF signaling pathway. Proteomic analysis highlighted disrupted TNF signaling and upregulated levels of TNFSF10 (TRAIL), TNFSF11 (RANKL), and TNFSF12 (TWEAK) in plasma of individuals with ASD. Single-cell RNA-seq revealed that B cells, CD4 T cells, and NK cells potentially contributed to these upregulations in ASD. Dysregulated TRAIL, RANKL, and TWEAK signaling pathways were specifically observed in CD8 T cells, CD4 T cells, and NK cells of individuals with ASD. These findings provide new insights into immune dysregulation mechanisms in ASD and highlight potential therapeutic targets.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Genes & Immunity<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41435-025-00349-z" target="_blank">https://dx.doi.org/10.1038/s41435-025-00349-z</a></p>2025-07-30T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41435-025-00349-zhttps://figshare.com/articles/journal_contribution/A_multi-omics_approach_reveals_dysregulated_TNF-related_signaling_pathways_in_circulating_NK_and_T_cell_subsets_of_young_children_with_autism/30971347CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/309713472025-07-30T09:00:00Z |
| spellingShingle | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism Wared Nour-Eldine (13904298) Biological sciences Genetics Biomedical and clinical sciences Immunology Neurosciences Autism Spectrum Disorder (ASD) Peripheral immune dysregulation Transcriptomics Proteomics Neuroimmunology |
| status_str | publishedVersion |
| title | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism |
| title_full | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism |
| title_fullStr | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism |
| title_full_unstemmed | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism |
| title_short | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism |
| title_sort | A multi-omics approach reveals dysregulated TNF-related signaling pathways in circulating NK and T cell subsets of young children with autism |
| topic | Biological sciences Genetics Biomedical and clinical sciences Immunology Neurosciences Autism Spectrum Disorder (ASD) Peripheral immune dysregulation Transcriptomics Proteomics Neuroimmunology |