Anti-CD83 Monoclonal antibody, clone IC26f [PE/Cy7®]

Introduction The broccoli isothiocyanate sulforaphane was shown to inhibit inflammation and tumor progression, also in pancreatic cancer, while its effect on tumor immunity is poorly understood. We investigated the immunoregulatory effect of sulforaphane on human dendritic cells alone and in presence of pancreatic tumor antigens, as well as underlying molecular mechanisms. Methods Sulforaphane-treated human dendritic cells were matured in vitro with a cytokine cocktail, and the expression of regulatory molecules was examined by flow cytometry. The subsequent T-cell response was analyzed by T-cell proliferation assay and CD25 expression. To confirm the findings, dendritic cells pulsed with pancreatic cancer-derived tumor antigens were used. To identify the involved pathway- and microRNA-signaling in sulforaphane-treated dendritic cells, inhibitors of various signaling pathways, western blot analysis, microRNA array, and bioinformatic analysis were applied. Results Sulforaphane modulated the expression of the costimulatory CD80, CD83 and the suppressive B7-H1 molecules on dendritic cells and thereby promoted activation of T cells. The effect was verified in presence of pancreatic tumor antigens. Phosphorylation of STAT3 in dendritic cells was diminished by sulforaphane, and the inhibition of JAK/STAT3 led to downregulation of B7-H1 expression. Among the identified top 100 significant microRNA candidates, the inhibition of miR-155-5p, important for the expression of costimulatory molecules, and the induction of miR-194-5p, targeting the B7-H1 gene, were induced by sulforaphane. Conclusion Our findings demonstrate that sulforaphane promotes T-cell activation by dendritic cells through the modulation of regulatory molecules, JAK/STAT3- and microRNA-signaling in healthy conditions and in context of pancreatic cancer-derived antigens. They explore the immunoregulatory properties of sulforaphane and justify further research on nutritional strategies in the co-treatment of cancer.

Rhipicephalus (Boophitus) microptus is the main cattle ectoparasite in tropical areas. Gir x Holstein crossbred cows are well adapted to different production systerns in Brazil. In this context, we performed genome-wide association study (GWAS) and post-GWAS analyses for R. microptus resistance in an experimental Gir x Holstein F-2 population. Single nucleotide polymorphisrns (SNP) identified in GWAS were used to build gene networks and to investigate the breed of origin for its alleles. Tick artificial infestations were performed during the dry and rainy seasons. Illurnina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA) and single-step BLUP procedure was used for GWAS. Post-GWAS analyses were performed by gene ontology terms enrichment and gene transcription factors networks, generated from enriched transcription factors, identified from the promoter sequences of selected gene sets. The genetic origin of marker alleles in the F-2 population was assigned using the breed of origin of alleles approach. Heritability estimates for tick counts were 0.40 +/- 0.11 in the rainy season and 0.54 +/- 0.11 in the dry season. The top ten 0.5-Mbp windows with the highest percentage of genetic variance explained by SNP markers were found in chromosomes 10 and 23 for both the dry and rainy seasons. Gene network analyses allowed the identification of genes involved with biological processes relevant to immune system functions (TREM1, TREM2, and CD8,9). Gene-transcription factors network allowed the identification of genes involved with immune functions (MY05A, TREML1, and PRSS16). In resistant animals, the average proportion of animals showing significant SNPs with paternal and maternal alleles originated from Gir breed was 44.8% whereas the proportion of animals with both paternal and maternal alleles originated from Holstein breed was 11.3%. Susceptible animals showing both paternal and maternal alleles originated from Holstein breed represented 44.6% on average, whereas both paternal and maternal alleles originated from Gir breed animals represented 9.3%. This study allowed us to identify candidate genes for tick resistance in Gir x Holstein crossbreds in both rainy and dry seasons. According to the origin of alleles analysis, we found that most animals classified as resistant showed 2 alleles from Gir breed, while the susceptible ones showed alleles from Holstein. Based on these results, the identified genes may be thoroughly investigated in additional experiments aiming to validate their effects on tick resistance phenotype in cattle.