Single-cell transcriptomics reveals macrophage-driven CD4+/CD8+ T cell differentiation via MIF/TNF signaling in Guillain-Barre syndrome

Guillain-Barre syndrome (GBS) is an autoimmune disorder characterized by acute peripheral demyelination, leading to progressive muscle weakness and sensory loss. While CD4+ T cells and macrophages are implicated in autoimmune neuropathies, the compositional dynamics and activation mechanisms of circulating immune cells remain elusive. Here, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMC) from 3 GBS patients and 2 healthy controls, coupled with integrative analysis of scRNA-seq data from murine inflammatory neuropathy models and longitudinal transcriptomes of rat GBS. Our results demonstrate that macrophages orchestrate CD4+/CD8+ T cell differentiation through MIF and TNF signaling axes, thereby propagating autoimmune neuroinflammation. Notably, MIF, C-C motif chemokine ligands (CCLs), and IL16 signaling pathways were significantly augmented in activated CD4+ T cells, with chemokines and tumor necrosis factor (TNF) exhibiting progressive upregulation during disease course. Collectively, we identify the MIF/TNF-driven T cell differentiation-chemokine secretion axis as a pathogenic hub in inflammatory neuropathy, revealing tractable targets for immunomodulatory interventions.