| First Author | Park H | Year | 2026 |
| Journal | Cell Rep | Volume | 45 |
| Issue | 4 | Pages | 117197 |
| PubMed ID | 41886452 | Mgi Jnum | J:389053 |
| Mgi Id | MGI:8321118 | Doi | 10.1016/j.celrep.2026.117197 |
| Citation | Park H, et al. (2026) Innate imprinting of transcriptional trajectories governs respiratory T(RM) fate and persistence. Cell Rep 45(4):117197 |
| abstractText | Respiratory T cell immunity wanes rapidly, and inducing durable mucosal memory remains a major challenge. We demonstrate that precision adjuvant activity, using distinct pattern recognition receptor (PRR) agonists to shape innate inflammation, imprints transcriptional trajectories that govern CD8 T cell fate. Using a nano-emulsion platform, Toll-like receptor (TLR)4 signaling induces neutrophilic inflammation and a C/EBP-NF-kappaB-HIF program that promotes durable, stem-like type 3 CD127(+) tissue-resident memory T cells (T(RM)s). Conversely, stimulator of interferon genes (STING) drives dendritic cell (DC)-monocytic inflammation and activates an IRF-STAT-T-bet axis that programs attrition-prone type 1 T(RM)s. We reconcile systemic and tissue divergence models by identifying distinct T(RM) precursors. During influenza, Ly6C(lo)PD-1(hi)LAG-3(hi)CD69(hi) precursors differentiate via local reprogramming (tissue divergence). In contrast, vaccination generates Ly6C(lo)LAG-3(lo)CD103(hi) precursors in lymph nodes and lungs that bypass inhibitory stages (systemic divergence). Mechanistically, T-bet limits T(RM) precursor formation and differentiation into long-lived type 3 T(RM)s. Thus, selecting precision adjuvants that limit T-bet activity is critical for durable mucosal T cell immunity. |
