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However, many aspects of M\u00fcller cell function remain poorly characterized. In this study, we reanalyzed a single-cell RNA-seq (scRNA-seq) dataset from Aire-\/- mice, focusing on M\u00fcller cells and T cells. We identified nine distinct M\u00fcller cell subgroups and five T cell subgroups, with activated M\u00fcller cells comprising the majority of the M\u00fcller cells in the inflamed retina. Using SCassist, an AI-based workflow assistant for single-cell analysis, we created a comparison matrix to quantify pathway involvement in each M\u00fcller cell subset. This approach unveils the functional dynamics of M\u00fcller cells during retinal inflammation. Activated M\u00fcller cells primarily exhibit enhanced inflammatory activity and adopt a macrophage or dendritic-cell-like phenotype, in the presence or absence of increased neuronal activity. These changes are primarily driven by Interferon Regulatory Factors (IRFs), acting alone or in concert with Neuronal Differentiation 1 (NEUROD1). We further inferred the interactions between M\u00fcller cells and T cells and found that activated M\u00fcller cells do not appear to exhibit extra chemoattraction to Th1 cells compared to other M\u00fcller cell subsets, but they do show such effects on the Th1-like regulatory T cells (Tregs). Activated M\u00fcller cells display nearly exclusive expression of immune checkpoint molecules, primarily targeting Th1 cells. These findings may uncover a previously unrecognized role for activated M\u00fcller cells in attenuating Th1 cell activity.<\/jats:p>","DOI":"10.1101\/2025.02.28.640907","type":"posted-content","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T07:41:01Z","timestamp":1741333261000},"source":"Crossref","is-referenced-by-count":0,"title":["AI-Driven Analysis Unveils Functional Dynamics of M\u00fcller Cells in Retinal Autoimmune Inflammation"],"prefix":"10.64898","author":[{"given":"Guangpu","family":"Shi","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, NIH, Bethesda 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-7172","authenticated-orcid":false,"given":"Vijayaraj","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, NIH, Bethesda 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7140-7671","authenticated-orcid":false,"given":"Rachel R.","family":"Caspi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Eye Institute, NIH, Bethesda 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041112344860000_2025.02.28.640907v3.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2021.07.007"},{"key":"2026041112344860000_2025.02.28.640907v3.2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.659843"},{"key":"2026041112344860000_2025.02.28.640907v3.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-111523-102000"},{"key":"2026041112344860000_2025.02.28.640907v3.4","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22477"},{"key":"2026041112344860000_2025.02.28.640907v3.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.07.001"},{"key":"2026041112344860000_2025.02.28.640907v3.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-03-00877.1996"},{"key":"2026041112344860000_2025.02.28.640907v3.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.07.017"},{"key":"2026041112344860000_2025.02.28.640907v3.8","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2021.815923"},{"key":"2026041112344860000_2025.02.28.640907v3.9","doi-asserted-by":"publisher","DOI":"10.1007\/BF00163549"},{"key":"2026041112344860000_2025.02.28.640907v3.10","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.123.7.1000"},{"key":"2026041112344860000_2025.02.28.640907v3.11","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(82)90069-1"},{"key":"2026041112344860000_2025.02.28.640907v3.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2013.01.004"},{"key":"2026041112344860000_2025.02.28.640907v3.13","doi-asserted-by":"publisher","DOI":"10.1097\/ICB.0b013e3181f7455d"},{"key":"2026041112344860000_2025.02.28.640907v3.14","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-75402-4_37"},{"key":"2026041112344860000_2025.02.28.640907v3.15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.140.5.1490"},{"key":"2026041112344860000_2025.02.28.640907v3.16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7414"},{"key":"2026041112344860000_2025.02.28.640907v3.17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2483"},{"key":"2026041112344860000_2025.02.28.640907v3.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1915571116"},{"key":"2026041112344860000_2025.02.28.640907v3.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-68401-y"},{"key":"2026041112344860000_2025.02.28.640907v3.20","doi-asserted-by":"crossref","unstructured":"Caspi, R.R. , F.G. 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