Zfp335 establishes eTreg lineage and neonatal immune tolerance by targeting Hadha-mediated fatty acid oxidation.

Regulatory T cells (Tregs) are instrumental in maintaining immune tolerance and preventing destructive autoimmunity, but how heterogeneous Treg populations are established remains largely unknown. Here, we show that Zfp335 deletion in Tregs failed to differentiate into effector Tregs (eTregs) and lose Treg-suppressive function and that KO mice exhibited early-onset lethal autoimmune inflammation with unrestricted activation of conventional T cells. Single-cell RNA-Seq analyses revealed that Zfp335-deficient Tregs lacked a eTreg population and showed dramatic accumulation of a dysfunctional Treg subset. Mechanistically, Zfp335-deficient Tregs displayed reduced oxidative phosphorylation and dysfunctional mitochondrial activity. Further studies revealed that Zfp335 controlled eTreg differentiation by regulating fatty acid oxidation (FAO) through direct targeting of the FAO enzyme Hadha. Importantly, we demonstrate a positive correlation between ZNF335 and HADHA expression in human eTregs. Our findings reveal that Zfp335 controls FAO-driven eTreg differentiation to establish immune tolerance.

Ecosystem service pattern of Fuzhou City based on ecosystem service bundles.

Based on InVEST model, recreational opportunity spectrum, factor analysis, cold and hot spot analysis, SOFM neural network, relief degree of land surface (RDLS) methods, we evalua-ted six kinds of ecosystem service in Fuzhou City and analyzed the trade-offs and synergies among them, with the aim to clarify the dominant services and the spatial pattern of service bundles in different topographical regions. The results showed substantial spatial heterogeneity in different ecosystem services of Fuzhou City. Water yield, carbon sequestration, habitat quality, and recreational opportunities were totally high, whereas the supply of agricultural products and soil and water conservation were low and substantial differences. The interaction between water yield and cultural servi-ces were synergies, but trade-offs occurred among regulating service, supporting service and agricultural products service. There were spatial aggregations for both trade-offs and synergies. Ecosystem service bundles could be divided into suburban recreation bundle, water conservation bundle, agricultural products bundle, urban life bundle, and forest ecological conservation bundle. The composition of service bundles clusters was different under different RDLS, with obvious spatial heterogeneity.