| First Author | Peng V | Year | 2024 |
| Journal | J Exp Med | Volume | 221 |
| Issue | 3 | PubMed ID | 38197946 |
| Mgi Jnum | J:352007 | Mgi Id | MGI:7665182 |
| Doi | 10.1084/jem.20230124 | Citation | Peng V, et al. (2024) Inositol phosphatase INPP4B sustains ILC1s and intratumoral NK cells through an AKT-driven pathway. J Exp Med 221(3) |
| abstractText | Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that coordinate early immune responses and maintain tissue homeostasis. Type 1 innate immune responses are mediated by natural killer (NK) cells and group 1 ILCs (ILC1s). Despite their shared features, NK cells and ILC1s display profound differences among various tissue microenvironments. Here, we identify the inositol polyphosphatase INPP4B as a hallmark feature of tissue-resident ILC1s and intratumoral NK cells using an scRNA-seq atlas of tissue-associated and circulating NK/ILC1s. Conditional deletion of Inpp4b in ILC1s and NK cells reveals that it is necessary for the homeostasis of tissue-resident ILC1s but not circulating NK cells at steady-state. Inpp4b-deficient cells display increased rates of apoptosis and reduced activation of the prosurvival molecule AKT. Furthermore, expression of Inpp4b by NK/ILC1s is necessary for their presence in the intratumoral environment, and lack of Inpp4b impairs antitumor immunity. These findings highlight INPP4B as a novel regulator of tissue residency and antitumor function in ILC1s and NK cells. |
