Research Note: Reducing the competition for feed to facilitate the mating of Heifers as yearlings

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Gene Expression Time Course in the Human Skin during Elicitation of Allergic Contact Dermatitis

Genes involved in the inflammatory response resulting in allergic contact dermatitis (ACD) are only partly known. In this study, we introduce the use of high-density oligonucleotide arrays for gene expression profiling in human skin during the elicitation of ACD. Skin biopsies from normal and nickel-exposed skin were obtained from seven nickel-allergic patients and five nonallergic controls at four different time points during elicitation of eczema. Each gene expression profile was analyzed by hybridization to high-density oligonucleotide arrays. Cluster analysis of 74 genes found to be differentially expressed in the patients over time revealed that the patient samples may be categorized into two groups: an early time-point group (no clinical reaction) and a late time-point group (clinical reaction). Bioinformatics analyses unraveled the potential involvement of signal transducers and activator of transcription and small/mothers against decepentaplegic (SMAD) transcription factors in the late time-point gene expression patterns. Concerning specific genes, the homeostatic chemokine CCL19 was unexpectedly found to be highly expressed in cells scattered in the deep dermis of the late time-point samples. Taken together, these findings suggest hitherto unknown roles of SMAD transcription factors and of CCL19 in the elicitation phase of ACD

β2-Adaptin is constitutively de-phosphorylated by serine/threonine protein phosphatase PP2A and phosphorylated by a staurosporine-sensitive kinase

AbstractClathrin-mediated endocytosis includes cycles of assembly and disassembly of the clathrin-coated vesicle constituents. How these cycles are regulated is still not fully known but previous studies have indicated that phosphorylation of coat subunits may play a role. Here we describe that β2-adaptin undergoes cycles of phosphorylation/de-phosphorylation in intact cells. Thus, β2-adaptin was constitutively de-phosphorylated by serine/threonine protein phosphatase 2A and phosphorylated by a staurosporine-sensitive kinase in vivo. Confocal laser scanning microscopy demonstrated that phosphorylated AP2 complexes were found more evenly distributed at the plasma membrane compared to non-phosphorylated AP2 complexes which were found in aggregates. Finally, we found that phosphorylation of β2-adaptin correlated with inhibition of clathrin-mediated endocytosis. Our results support the hypothesis that phosphorylation/de-phosphorylation of coat proteins plays a regulatory role in the assembly/disassembly cycle of clathrin-coated vesicles

Butyrate and propionate inhibit antigen-specific CD8⁺ T cell activation by suppressing IL-12 production by antigen-presenting cells

Abstract Short chain fatty acids (SCFAs), such as acetate, butyrate and propionate, are products of microbial macronutrients fermentation that distribute systemically and are believed to modulate host immune responses. Recent data have indicated that certain SCFAs, such as butyrate and propionate, directly modulate human dendritic cell (DC) function. Given the role of DCs in initiating and shaping the adaptive immune response, we now explore how SCFAs affect the activation of antigen-specific CD8+ T cells stimulated with autologous, MART1 peptide-pulsed DC. We show that butyrate reduces the frequency of peptide-specific CD8+ T cells and, together with propionate, inhibit the activity of those cells. On the contrary, acetate does not affect them. Importantly, butyrate and propionate inhibit the production of IL-12 and IL-23 in the DCs and exogenous IL-12 fully restores the activation of the MART-1-specific CD8+ T cells, whereas IL-23 has no effect. In conclusion, these results point to a pivotal role of butyrate and propionate in modulating CD8+ T cell activation via the inhibition of IL-12 secretion from DCs. These findings reveal a novel mechanism whereby bacterial fermentation products may modulate CD8+ T cell function with possible implications in anti-cancer immunotherapy

Activated human CD4+ T cells express transporters for both cysteine and cystine

Because naïve T cells are unable to import cystine due to the absence of cystine transporters, it has been suggested that T cell activation is dependent on cysteine generated by antigen presenting cells. The aim of this study was to determine at which phases during T cell activation exogenous cystine/cysteine is required and how T cells meet this requirement. We found that early activation of T cells is independent of exogenous cystine/cysteine, whereas T cell proliferation is strictly dependent of uptake of exogenous cystine/cysteine. Naïve T cells express no or very low levels of both cystine and cysteine transporters. However, we found that these transporters become strongly up-regulated during T cell activation and provide activated T cells with the required amount of cystine/cysteine needed for T cell proliferation. Thus, T cells are equipped with mechanisms that allow T cell activation and proliferation independently of cysteine generated by antigen presenting cells