Schuijs, Martijn J. and Png, Shaun and Richard, Arianne C. and Tsyben, Anastasia and Hamm, Gregory and Stockis, Julie and Garcia, Celine and Pinaud, Silvain and Nicholls, Ashley and Ros, Xavier Romero and Su, Jing and Eldridge, Matthew D. and Riedel, Angela and Serrao, Eva M. and Rodewald, Hans-Reimer and Mack, Matthias and Shields, Jacqueline D. and Cohen, E. Suzanne and McKenzie, Andrew N. J. and Goodwin, Richard J. A. and Brindle, Kevin M. and Marioni, John C. and Halim, Timotheus Y. F. (2020) ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung. NATURE IMMUNOLOGY, 21 (9). 998-+. ISSN 1529-2908, 1529-2916
Full text not available from this repository. (Request a copy)Abstract
Metastasis constitutes the primary cause of cancer-related deaths, with the lung being a commonly affected organ. We found that activation of lung-resident group 2 innate lymphoid cells (ILC2s) orchestrated suppression of natural killer (NK) cell-mediated innate antitumor immunity, leading to increased lung metastases and mortality. Using multiple models of lung metastasis, we show that interleukin (IL)-33-dependent ILC2 activation in the lung is involved centrally in promoting tumor burden. ILC2-driven innate type 2 inflammation is accompanied by profound local suppression of interferon-gamma production and cytotoxic function of lung NK cells. ILC2-dependent suppression of NK cells is elaborated via an innate regulatory mechanism, which is reliant on IL-5-induced lung eosinophilia, ultimately limiting the metabolic fitness of NK cells. Therapeutic targeting of IL-33 or IL-5 reversed NK cell suppression and alleviated cancer burden. Thus, we reveal an important function of IL-33 and ILC2s in promoting tumor metastasis via their capacity to suppress innate type 1 immunity. Pathological group 2 innate lymphoid cells (ILC2s) have mainly been implicated in allergy. Halim and colleagues demonstrate that ILC2s orchestrate a prometastatic pathway via the recruitment of eosinophils that suppress NK cell function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RNA-SEQ EXPERIMENTS; T-CELLS; LYMPHOID-CELLS; EXPRESSION; METASTASIS; TISSUE; INTERLEUKIN-33; RECRUITMENT; ACTIVATION; INITIATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Mar 2021 09:04 |
| Last Modified: | 17 Mar 2021 09:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44061 |
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