| First Author | Vanderkerken M | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 5 | PubMed ID | 33724364 |
| Mgi Jnum | J:315099 | Mgi Id | MGI:6724820 |
| Doi | 10.1084/jem.20190835 | Citation | Vanderkerken M, et al. (2021) ILC3s control splenic cDC homeostasis via lymphotoxin signaling. J Exp Med 218(5) |
| abstractText | The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTalpha1beta2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpalpha+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpalpha+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpalpha+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTbetaR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTalpha1beta2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis. |
