RESUMO
Group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function. Recent studies have investigated the role of the mammalian target of rapamycin complex (mTOR) in ILC3s, whereas the mTORC1-related mechanisms and crosstalk between mTORC1 and mTORC2 involved in regulating ILC3 homeostasis remain unknown. In this study, we found that mTORC1 but not mTORC2 was critical in ILC3 development, IL-22 production, and ILC3-mediated intestinal homeostasis. Single-cell RNA sequencing revealed that mTORC1 deficiency led to disruption of ILC3 heterogeneity, showing an increase in differentiation into ILC1-like phenotypes. Mechanistically, mTORC1 deficiency decreased the expression of NFIL3, which is a critical transcription factor responsible for ILC3 development. The activities of both mTORC1 and mTORC2 were increased in wild-type ILC3s after activation by IL-23, whereas inhibition of mTORC1 by Raptor deletion or rapamycin treatment resulted in increased mTORC2 activity. Previous studies have demonstrated that S6K, the main downstream target of mTORC1, can directly phosphorylate Rictor to dampen mTORC2 activity. Our data found that inhibition of mTORC1 activity by rapamycin reduced Rictor phosphorylation in ILC3s. Reversing the increased mTORC2 activity via heterozygous or homozygous knockout of Rictor in Raptor-deleted ILC3s resulted in severe ILC3 loss and complete susceptibility to intestinal infection in mice with mTORC1 deficiency (100% mortality). Thus, mTORC1 acts as a rheostat of ILC3 heterogeneity, and mTORC2 protects ILC3s from severe loss of cells and immune activity against intestinal infection when mTORC1 activity is diminished.
Assuntos
Imunidade Inata , Linfócitos , Camundongos , Animais , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Proteína Regulatória Associada a mTOR/genética , Fatores de Transcrição/metabolismo , Sirolimo/farmacologia , Mamíferos/metabolismoRESUMO
PURPOSE: The purpose of this in vitro study was to measure the color difference(â³E) on titanium alloy background and translucency parameter(TP) of four kinds of zirconia-based all-ceramic specimens, providing a clinical reference for restoring grayish abutment. METHODS: Four groups with a total of 24 ceramic specimens were fabricated to a final specimen dimension of 14 mm×14 mm×1.5 mm, two kinds of zirconia with different translucencyï¼Beitefu high-translucency, Cercon low-translucencyï¼and their corresponding body porcelain at the shade of A2 were used as followed:high-translucency zirconia sintered dentine porcelain(Group A),low-translucency zirconia sintered dentine porcelain(Group B),high-translucency zirconia sintered opaque and dentine porcelain(Group C),low-translucency zirconia sintered opaque and dentine porcelain(Group D).The color parameters of the specimens under two backgrounds (titanium alloy and shade A3 light-activated resin-based composite) were measured by Shade Eye NCC colorimeter, then the â³E value was determined by the relevant equations. The color parameters under black and white background were measured, and TP value was calculated. The experimental data were analyzed with SPSS 17.0 software package. RESULTS: There was significant difference of the TP value and the â³E value among four groups specimens(Pï¼0.05), the TP value was arranged as follows: group Dï¼group Cï¼group Bï¼group A. The specimen used with opaque porcelain showed significantly reduced translucency. The â³E value was arranged as follows: group D ï¼ group C ï¼ group B ï¼ 1.5 ï¼ 2 ï¼group A, the â³E value of group A cannot be accepted in clinic. CONCLUSIONS: The restoration of low-translucency zirconia sintered translucency veneering ceramic has better translucency, with value of â³Eï¼1.5 when used on the grayish abutment, which has a good aesthetic performance.
