Splenic TNF-α signaling potentiates the innate-to-adaptive transition of antiviral NK cells Journal Article
| Authors: | Mujal, A. M.; Owyong, M.; Santosa, E. K.; Sauter, J. C.; Grassmann, S.; Pedde, A. M.; Meiser, P.; Wingert, C. K.; Pujol, M.; Buchholz, V. R.; Lau, C. M.; Böttcher, J. P.; Sun, J. C. |
| Article Title: | Splenic TNF-α signaling potentiates the innate-to-adaptive transition of antiviral NK cells |
| Abstract: | Natural killer (NK) cells possess both innate and adaptive features. Here, we investigated NK cell activation across tissues during cytomegalovirus infection, which generates antigen-specific clonal expansion and long-lived memory responses. Longitudinal tracking and single-cell RNA sequencing of NK cells following infection revealed enhanced activation in the spleen, as well as early formation of a CD69lo precursor population that preferentially gave rise to adaptive NK cells. Splenic NK cells demonstrated heightened tumor necrosis factor alpha (TNF-α) signaling and increased expression of the receptor TNFR2, which coincided with elevated TNF-α production by splenic myeloid cells. TNFR2-deficient NK cells exhibited impaired interferon gamma (IFN-γ) production and expansion. TNFR2 signaling engaged two distinct nuclear factor κB (NF-κB) signaling arms—innate effector NK cell responses required canonical NF-κB signaling, whereas non-canonical NF-κB signaling enforced differentiation of CD69lo adaptive NK cell precursors. Thus, NK cell priming in the spleen during viral infection promotes an innate-to-adaptive transition, providing insight into avenues for generating adaptive NK cell immunity across diverse settings. © 2025 Elsevier Inc. |
| Keywords: | nk cells; tnf-α; mcmv; nf-κb signaling; nik; tnfr2 |
| Journal Title: | Immunity |
| Volume: | 58 |
| Issue: | 3 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2025-03-11 |
| Start Page: | 585 |
| End Page: | 600.e6 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2025.02.012 |
| PUBMED: | 40023159 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding authors are Source: Scopus Adriana Mujal and Joseph Sun -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work