Spatial and Functional Regulation of Human Chronic Inflammation by Dendritic cells

Le 17 juin 2026 à 08h30 Séminaire

Chronic immune-mediated inflammatory diseases share poorly understood tissue-level mechanisms that drive persistence and treatment resistance. Here, using single-cell RNA sequencing, flow cytometry, and spatial transcriptomics across human cervical lymph nodes, Crohn's disease, ulcerative colitis, rheumatoid arthritis, and sarcoidosis, we identify a conserved inflammatory activated DC2 state (iaDC) as the central organising unit of chronic inflammation. iaDCs are induced from DC2s by IFNγ through JAK–STAT signalling and localise within spatially conserved niches co-enriched for CXCL9⁺ monocytes and effector memory CD4⁺ and CD8⁺ T cells. iaDC-conditioned DCs drive IFNγ-producing effector T-cell responses, consistent with a feed-forward inflammatory circuit. iaDC abundance and niche organisation associate with disease activity, anti-TNFα resistance, and response to JAK inhibition across diseases. These findings identify a conserved, spatially organised iaDC-centred inflammatory circuit as a shared pathogenic mechanism and tractable therapeutic target across chronic inflammatory diseases.