論文 - 詳細
| RRC ID | 89543 |
|---|---|
| 著者 | Xing Y, Reznikov I, Ahmed AN, Sidhu I, Wisnewski J, Farhat A, Prystupa A, Konieczny P, Mansfield K, Cooper ML, Yeung ST, Kim M, Adeghe S, Gaines KD, Manson M, Sim JH, Huang Q, Moshiri AS, Khanna KM, Lu TT, Guttman-Yassky E, Lund AW, Anandasabapathy N, Naik S. |
| タイトル | Peripheral immune-inducer dendritic cells drive early-life allergic inflammation. |
| ジャーナル | Nature |
| Abstract |
Atopic diseases associated with allergens, as well as allergic diseases, frequently arise early in life; however, the age-dependent mechanisms governing immune responses to allergens remain poorly understood1. Here we find that in early life, exposure to common allergens triggers a distinct bifurcated immune response, simultaneously triggering type 17 inflammation in the skin and initiating canonical T helper 2 sensitization in the lymph nodes. This early-life γδ type 17-mediated dermatitis primes the exaggerated allergic lung inflammation upon secondary allergen exposure. Mechanistically, we find dendritic cell (DC)-mediated type 17 activation directly in the skin without requiring migration to lymph nodes; we term this state 'peripheral immune inducer' (pii) DC. CD301b+ conventional type 2 DCs acquire allergen, adopt the pii-DC state, produce IL-23 and activate local γδ type 17 cells independently of lymph-node engagement. The pii-DC state is enabled by the immature hypothalamic-pituitary-adrenal axis and physiologically low systemic glucocorticoids characteristic of early life2,3; DC-specific deletion of the glucocorticoid receptor recapitulates the pii-DC phenotype. These findings define a developmental checkpoint, set by neuroendocrine maturation, that enables in situ DC activation and immune induction, thereby shaping age-dependent responses to allergens. |
| 巻・号 | 652(8112) |
| ページ | 1308-1317 |
| 公開日 | 2026-4-1 |
| DOI | 10.1038/s41586-026-10162-x |
| PII | 10.1038/s41586-026-10162-x |
| PMID | 41741647 |
| PMC | PMC13036635 |
| MeSH | Allergens / immunology Animals Dendritic Cells* / cytology Dendritic Cells* / immunology Dermatitis, Atopic / immunology Dermatitis, Atopic / pathology Female Hypersensitivity* / immunology Hypersensitivity* / pathology Inflammation* / immunology Inflammation* / pathology Interleukin-23 / biosynthesis Interleukin-23 / immunology Lung / immunology Lung / pathology Lymph Nodes / cytology Lymph Nodes / immunology Male Mice Mice, Inbred C57BL Receptors, Antigen, T-Cell, gamma-delta / immunology Skin / immunology Skin / pathology Th17 Cells / immunology Th2 Cells / immunology |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 102 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 106.8 |
| リソース情報 | |
| 実験動物マウス | RBRC04395 |