Nat Immunol. 2024 Oct 11. doi: 10.1038/s41590-024-01986-8. Online ahead of print.
ABSTRACT
The mechanisms that guide T helper 2 (TH2) cell differentiation in barrier tissues are unclear. Here we describe the molecular pathways driving allergen-specific TH2 cells using temporal, spatial and single-cell transcriptomic tracking of house dust mite-specific T cells in mice. Differentiation and migration of lung allergen-specific TH2 cells requires early expression of the transcriptional repressor Blimp-1. Loss of Blimp-1 during priming in the lymph node ablated the formation of TH2 cells in the lung, indicating early Blimp-1 promotes TH2 cells with migratory capability. IL-2/STAT5 signals and autocrine/paracrine IL-10 from house dust mite-specific T cells were essential for Blimp-1 and subsequent GATA3 upregulation through repression of Bcl6 and Bach2. Spatial microniches of IL-2 in the lymph node supported the earliest Blimp-1+TH2 cells, demonstrating lymph node localization is a driver of TH2 initiation. Our findings identify an early requirement for IL-2-mediated spatial microniches that integrate with allergen-driven IL-10 from responding T cells to drive allergic asthma.
PMID:39394532 | DOI:10.1038/s41590-024-01986-8
