PDCD5 regulates iNKT cell terminal maturation and iNKT1 fate decision

Invariant natural killer T1(iNKT1)cells are characterized by the preferential expression of T-box transcription factor T-bet(encoded by Tbx21)and the production of cytokine IFN-γ,but the relationship between the developmental process and iNKT1 lineage diversification in the thymus remains elusive.We report in the present study a crucial role of programmed cell death 5(PDCD5)in iNKT cell terminal maturation and iNKT1 fate determination.Mice with T cell-specific deletion of PDCD5 had decreased numbers of thymic and peripheral iNKT cells with a predominantly immature phenotype and defects in response toα-galactosylceramide.Loss of PDCD5 also selectively abolished the iNKT1 lineage by reducing T-bet expression in iNKT cells at an early thymic developmental stage(before CD44 upregulation).We further demonstrated that TOX2,one of the high mobility group proteins that was highly expressed in iNKT cells at stage 1 and could be stabilized by PDCD5,promoted the permissive histone H3K4me3 modification in the promoter region of Tbx21.These data indicate a pivotal and unique role of PDCD5/TOX2 in iNKT1 lineage determination.They also suggest that the fate of iNKT1 may be programmed at the developmental stage of iNKT cells in the thymus.

TRAF3IP3 at the trans-Golgi network regulates NKT2 maturation via the MEK/ERK signaling pathway

Thymic natural killer T(NKT)2 cells are a subset of invariant NKT cells with PLZF^(hi)GATA3^(hi)IL-4^(+).The differentiation of NKT2 cells is not fully understood.In the present study,we report an important role of TRAF3-interacting protein 3(TRAF3IP3)in the functional maturation and expansion of committed NKT2s in thymic medulla.Mice with T-cell-specific deletion of TRAF3IP3 had decreased thymic NKT2 cells,decreased IL-4-producing peripheral iNKTs,and defects in response toα-galactosylceramide.Positive selection and high PLZF expression in CD24^(+)CD44^(−) and CCR7^(+)CD44^(−) immature iNKTs were not affected.Only CD44^(hi)NK1.1^(−) iNKTs in Traf3ip3^(−/−) mice showed reduced expression of Egr2,PLZF,and IL-17RB,decreased proliferation,and reduced IL-4 production upon stimulation.This Egr2 and IL-4 expression was augmented by MEK1/ERK activation in iNKTs,and TRAF3IP3 at the trans-Golgi network recruited MEK1 and facilitated ERK phosphorylation and nuclear translocation.LT βR-regulated bone marrow-derived nonlymphoid cells in the medullary thymic microenvironment were required for MEK/ERK activation and NKT2 maturation.These data demonstrate an important functional maturation process in NKT2 differentiation that is regulated by MEK/ERK signaling at the trans-Golgi network.

Discontinuous streaming potential via liquid gate

Streaming potential is mainly related to electrokinetic energy conversion,which has been considered to show promising potential for advanced technologies,especially sensing.The inherent property of streaming potential is that the energy conversion process is always a continuous state.However,practical applications include many cases of discontinuous states,such as nonlinear sensing.Here,we report a discontinuous streaming potential electrokinetic energy conversion fluid system.Experiments and theoretical calculations reveal that this system exhibits a discontinuous electrokinetic effect and provides a gating liquid slip in micropores,offering the advantages of gating liquid charge coupling and interfacial drag reduction.Moreover,the system is demonstrated in a wearable fall-down alert application.We expect this liquid gating energy conversion system to open up a platform for the design and application of autonomous health monitoring devices,seismic sea wave warning systems,and beyond.