biostudies-literatureUnknown15(18)Fan SSAutoimmune diseases are driven by a breach of self-tolerance, leading to chronic inflammation and organ damage. While the Th1 and Th17 paradigms have long dominated our understanding of T-cell-mediated pathology, a distinct subset of CD4⁺ T helper cells defined by the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as a central and non-redundant pathogenic driver. These GM-CSF-producing Th cells orchestrate autoimmune pathology across a spectrum of diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, among others. Mechanistically, they act as critical amplifiers of inflammation by activating and recruiting myeloid cells, which in turn mediate tissue destruction. Furthermore, they establish vicious feedback loops, Theranostics9944-9968https://www.ebi.ac.uk/biostudies/studies/S-EPMC12486991biostudies-literatureGM-CSF<sup>+</sup> Th: a central player in autoimmunity.PMC12486991Fan SSLiu YMeng XYLuo YBXu XfalseGM-CSF<sup>+</sup> Th: a central player in autoimmunity.Autoimmune diseases are driven by a breach of self-tolerance, leading to chronic inflammation and organ damage. While the Th1 and Th17 paradigms have long dominated our understanding of T-cell-mediated pathology, a distinct subset of CD4⁺ T helper cells defined by the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as a central and non-redundant pathogenic driver. These GM-CSF-producing Th cells orchestrate autoimmune pathology across a spectrum of diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, among others. Mechanistically, they act as critical amplifiers of inflammation by activating and recruiting myeloid cells, which in turn mediate tissue destruction. Furthermore, they establish vicious feedback loops, 2025-01-01T00:00:00Z20252026-07-15T09:47:23.727Z2026-07-02T03:12:37.936ZS-EPMC124869914104107710.7150/thno.121766