論文 - 詳細
| RRC ID | 86313 |
|---|---|
| 著者 | Verwaerde S, Hastir JF, Schetters STT, Smole U, Seys L, Baptista AP, English K, Schuijs MJ, Aegerter H, Van Damme KFA, Bugler-Lamb A, Gerebtsov N, Toussaint W, Ban T, Tamura T, Ginhoux F, Liu Z, Saelens W, Hammad H, Guilliams M, Lambrecht BN. |
| タイトル | Innate type 2 lymphocytes trigger an inflammatory switch in alveolar macrophages. |
| ジャーナル | Immunity |
| Abstract |
Tissue-resident alveolar macrophages (trAMs) safeguard gas exchange by restraining inflammation. Compared with recruited alveolar macrophages (recAMs), trAMs are considered more immunoregulatory and resilient to inflammatory reprogramming. Using a mouse model enabling selective trAM depletion and replacement, we uncovered a pro-inflammatory role for trAMs during type 2 immunity. Upon allergen exposure, interleukin-33-activated innate type 2 lymphoid cells (ILC2s) produced interleukin-13, which reprogrammed trAMs through induction of the transcription factor interferon regulatory factor 4 (IRF4). IRF4 suppressed the expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and dismantled the PPARγ-dependent homeostatic regulon that defines trAM identity, while initiating a transcriptional program driving chemokine production and cell fusion. This resulted in the recruitment of granulocytes, ILC2s, and regulatory T cells, as well as the formation of multinucleated giant cells in the alveolar niche. Thus, a PPARγ-to-IRF4 switch reconfigures trAMs into pro-inflammatory effectors, promoting allergen-induced lung pathology. |
| 公開日 | 2025-12-11 |
| DOI | 10.1016/j.immuni.2025.11.015 |
| PII | S1074-7613(25)00517-5 |
| PMID | 41386231 |
| IF | 22.553 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 84 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 1.2 |
| リソース情報 | |
| 実験動物マウス | RBRC04395 |