Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. While SRC1 inhibits the differentiation of regulatory T cells (T regs ) critical for establishing immune tolerance, we show here that SRC2 stimulates T reg differentiation. SRC2 is dispensable for the development of thymic T regs , whereas naive CD4 + T cells from mice deficient of SRC2 specific in T regs ( SRC2 fl/fl /Foxp3 YFP-Cre ) display defective T reg differentiation. Furthermore, the aged SRC2 fl/fl /Foxp3 YFP-Cre mice spontaneously develop autoimmune phenotypes including enlarged spleen and lung inflammation infiltrated with IFNγ-producing CD4 + T cells. SRC2 fl/fl /Foxp3 YFP-Cre mice also develop severer experimental autoimmune encephalomyelitis (EAE) due to reduced T regs . Mechanically, SRC2 recruited by NFAT1 binds to the promoter and activates the expression of Nr4a2 , which then stimulates Foxp3 expression to promote T reg differentiation. Members of SRC family coactivators thus play distinct roles in T reg differentiation and are potential drug targets for controlling immune tolerance.
Three commercial proteases, namely Protamex, Neutrase, and Alcalase were applied to treat palm kernel (PK) powders with the aim to modify the flavor of palm kernel oil (PKO) obtained from roasted PK. The results showed that after protease treatment and roasting, the volatile profile of obtained PKO was significantly modified with more pyrazines and other N‐heterocyclic compounds being formed. Protamex, among others, was especially effective in enhancing the generation of such N‐heterocyclic compounds. Besides, aroma‐active compounds such as benzeneacetaldehyde, 1‐(2‐furanyl)‐ethanone and 5‐methyl‐2‐furancarboxaldehyde were found at higher levels in protease‐treated PKO, whereas the content of 2‐furanmethanol decreased. On the basis of all pyrazines and other aroma‐active compounds, principal component analysis (PCA) clearly separated the protease‐treated PKOs from their respective control, with the volatile profile of PKOs derived from Protamex‐ and Alcalase‐treated PK being the most distinct. Practical applications The flavor quality is an important factor to edible oils which determines their application and acceptability to a large extent. For a long time, PKO is used as non‐flavor related fat base in food areas. The results in this study suggest that it is possible to use proteases to pretreat PK to modulate the flavor of PKO. The improvement in flavor would not only be beneficial for the current utilization of PKO, especially in bakery and confectionery areas, but also widen the scope of its applications. Besides, protease pretreatment combined with the thermal reactions as a novel approach might also be applied to modulate the flavor of other seeds’ oils with or without adaption.
Nuclear receptor coactivator 2 (Ncoa2) is a member of the Ncoa family of co-activators, and we previously showed that Ncoa2 regulates the differentiation of induced regulatory T cells. However, it remains unknown if Ncoa2 plays a role in CD8+ T-cell function. Here, we show that Ncoa2 promotes CD8+ T cell-mediated immune responses against tumors by stimulating T-cell activation via upregulating PGC-1α expression to enhance mitochondrial function. Mice deficient in Ncoa2 in T cells (Ncoa2fl/fl/CD4Cre) displayed defective immune responses against implanted MC38 tumors, which associated with significantly reduced tumor-infiltrating CD8+ T cells and decreased IFNγ production. Consistently, CD8+ T cells from Ncoa2fl/fl/CD4Cre mice failed to reject tumors after adoptive transfer into Rag1-/- mice. Further, in response to TCR stimulation, Ncoa2fl/fl/CD4Cre CD8+ T cells failed to increase mitochondrial mass, showed impaired oxidative phosphorylation, and had lower expression of PGC-1α, a master regulator of mitochondrial biogenesis and function. Mechanically, T cell activation-induced phosphorylation of CREB triggered the recruitment of Ncoa2 to bind to enhancers, thus, stimulating PGC-1α expression. Forced expression of PGC-1α in Ncoa2fl/fl/CD4Cre CD8+ T cells restored mitochondrial function, T-cell activation, IFNγ production, and anti-tumor immunity. This work informs the development of Ncoa2-based therapies that modulate CD8+ T cell-mediated anti-tumor immune responses.
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