Biology subjects

Merz, L.

Publications and source records attributed to Merz, L..

2 recordsLinked to original sources

bioRxiv2026

Prolonged TGF-β locks NK cells in a dysfunctional state through persistent epigenetic remodeling of IRF, T-bet and EOMES binding sites

TGF-{beta} signaling is a major regulator of immune cell differentiation and function, yet whether prolonged signaling can durably imprint dysfunctional immune states independently of continued pathway engagement remains unclear. Here, we identify signal duration as a critical determinant of human natural killer (NK) cell fate: short-term TGF-{beta} exposure induces largely reversible transcriptional, chromatin and functional changes, whereas prolonged exposure establishes persistent effector dysfunction independent of continued signaling. Mechanistically, prolonged TGF-{beta} drives durable loss of chromatin accessibility at effector-associated regulatory elements, particularly those enriched for IRF, EOMES, and T-bet binding motifs, resulting in stable restriction of NK cell effector programs despite reversibility of active histone marks. In contrast, tissue residency-associated programs remain largely reversible, revealing that distinct NK cell fate programs differ fundamentally in their susceptibility to epigenetic fixation downstream of the same cytokine signal. SMAD4 CUT&RUN and knockout experiments further demonstrate that canonical TGF-{beta} signaling acts primarily through rewiring of upstream transcriptional regulatory networks rather than direct targeting of effector loci. Finally, NK cells from patients with hepatocellular carcinoma recapitulate key functional and epigenetic features of the persistent TGF-{beta}-associated state defined in vitro. Together, these findings identify signal duration as a critical determinant of TGF-{beta}-driven cell fate and demonstrate that prolonged TGF-{beta} exposure can induce epigenetically stabilized dysfunctional states that persist after signal withdrawal, with important implications for therapeutic strategies aimed at reversing chronic TGF-{beta}-mediated dysfunction.

immunology↗

bioRxiv2021

Tolerance of Wildlife in Protected Area Borderlands

Increases in human-wildlife conflict globally threaten human wellbeing and biodiversity conservation. Sustainable solutions that promote coexistence of people and wildlife are needed, especially in human-dominated landscapes surrounding protected areas. Peoples attitudes toward wildlife influence their behaviours, including tolerance for human-wildlife interactions, poaching, and habitat degradation. Better understanding of how to improve peoples attitudes toward wildlife is instrumental to promoting coexistence between people and wildlife in shared spaces. Efforts to promote coexistence often fail because they are based on the inaccurate assumption that peoples attitudes towards wildlife are directly and proportionally related to wildlife-based financial incentives and costs. In reality, peoples attitudes towards wildlife are far more complex. We analysed surveys (n=237) from Mozambique to examine peoples attitudes toward wildlife in the buffer zones surrounding protected areas using logistic regression and Getis-Ord hot-spot analysis (GI*). Mozambique, which is under-represented in the wildlife-based research literature, is characterized by extreme poverty and rewilding efforts. We found that most respondents were tolerant of wildlife and tolerance was positively correlated with peoples age, gender, and agreement with rules governing wildlife conservation. Peoples tolerance for wildlife was also reinforced if they receive benefits from wildlife and are situated further from the park fence. Predation, human harm, and crop loss were not significant predictors of tolerance. We found no evidence of spatial patterns in tolerance for wildlife. Our results suggest that wildlife conservation programs are more likely to be successful if benefits are distributed equitably and community members are actively involved in decision making.

ecology↗