| First Author | He K | Year | 2024 |
| Journal | Nat Immunol | Volume | 25 |
| Issue | 11 | Pages | 2124-2139 |
| PubMed ID | 39394532 | Mgi Jnum | J:361012 |
| Mgi Id | MGI:7855099 | Doi | 10.1038/s41590-024-01986-8 |
| Citation | He K, et al. (2024) Spatial microniches of IL-2 combine with IL-10 to drive lung migratory T(H)2 cells in response to inhaled allergen. Nat Immunol 25(11):2124-2139 |
| abstractText | The mechanisms that guide T helper 2 (T(H)2) cell differentiation in barrier tissues are unclear. Here we describe the molecular pathways driving allergen-specific T(H)2 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 T(H)2 cells requires early expression of the transcriptional repressor Blimp-1. Loss of Blimp-1 during priming in the lymph node ablated the formation of T(H)2 cells in the lung, indicating early Blimp-1 promotes T(H)2 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(+)T(H)2 cells, demonstrating lymph node localization is a driver of T(H)2 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. |
