Abatacept (Cytotoxic T Lymphocyte Antigen 4-Fragment Crystallizable) Reduces Allergic Inflammation of Ovalbumin-Sensitized Mice.

Background Abatacept (Aba) is a cytotoxic T-lymphocyte antigen-4 and fragment crystallizable fusion protein. Aba blocks B7/Cluster of differentiation 28 - cytotoxic T-lymphocyte antigen-4 costimulatory pathway, inhibits cluster of differentiation 4+ T-cell activation, and is used as an anti-inflammatory drug. Objectives We conducted this study to assess the effectiveness of Aba in the treatment of allergic rhinitis (AR) in a mouse model. Methods We divided 40 four-week-old BALB/c mice into four groups: control group ( n = 10), positive control group (AR, n = 10), Aba group (AR + Aba, n = 10), and dexamethasone group (AR + Dex, n = 10). Mice in each group were challenged intranasally with daily ovalbumin (OVA) administration. Episodes of sneezing and nose rubbing were counted. Mice were sacrificed on day 42 and cytokines were measured in nasal lavage fluid. Nasal mucosae of five mice from each group were used for reverse transcriptase-polymerase chain reaction and western blot assay. Samples were collected from five mice from each group for histological analysis. Results Symptoms of AR significantly improved in the AR + Aba and AR + Dex groups compared with the AR group. Fewer eosinophils and goblet cells were seen in the AR + Aba and AR + Dex groups compared with the AR group. Both the AR + Aba and AR + Dex groups showed a significant decrease in nasal T helper 2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13 and T cell activation related IL-17A, and interferon gamma (IFN- γ). Total immunoglobulin (Ig) E and OVA-specific IgG1 levels were also significantly lower in the AR + Aba and AR + Dex groups. OVA-specific IgE level was also significantly lower in the AR + Aba than AR group. Conclusions Aba suppresses allergic inflammation and appears to be a good treatment for AR.

Comprehensive RNA sequencing in primary murine keratinocytes and fibroblasts identifies novel biomarkers and provides potential therapeutic targets for skin-related diseases

Background Keratinocytes and fibroblasts represent the major cell types in the epidermis and dermis of the skin and play a significant role in maintenance of skin homeostasis. However, the biological characteristics of keratinocytes and fibroblasts remain to be elucidated. The purpose of this study was to compare the gene expression pattern between keratinocytes and fibroblasts and to explore novel biomarker genes so as to provide potential therapeutic targets for skin-related diseases such as burns, wounds, and aging. Methods Skin keratinocytes and fibroblasts were isolated from newborn mice. To fully understand the heterogeneity of gene expression between keratinocytes and fibroblasts, differentially expressed genes (DEGs) between the two cell types were detected by RNA-seq technology. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the known genes of keratinocytes and fibroblasts and verify the RNA-seq results. Results Transcriptomic data showed a total of 4309 DEGs (fold-change > 1.5 and q-value < 0.05). Among them, 2197 genes were highly expressed in fibroblasts and included 10 genes encoding collagen, 16 genes encoding transcription factors, and 14 genes encoding growth factors. Simultaneously, 2112 genes were highly expressed in keratinocytes and included 7 genes encoding collagen, 14 genes encoding transcription factors, and 8 genes encoding growth factors. Furthermore, we summarized 279 genes specifically expressed in keratinocytes and 33 genes specifically expressed in fibroblasts, which may represent distinct molecular signatures of each cell type. Additionally, we observed some novel specific biomarkers for fibroblasts such as Plac8 (placenta-specific 8), Agtr2 (angiotensin II receptor, type 2), Serping1 (serpin peptidase inhibitor, clade G, member 1), Ly6c1 (lymphocyte antigen 6 complex, locus C1), Dpt (dermatopontin), and some novel specific biomarkers for keratinocytes such as Ly6a (lymphocyte antigen 6 complex, locus A) and Lce3c (late cornified envelope 3C), Ccer2 (coiled-coil glutamate-rich protein 2), Col18a1 (collagen, type XVIII, alpha 1) and Col17a1 (collagen type XVII, alpha 1). In summary, these data provided novel identifying biomarkers for two cell types, which can provide a resource of DEGs for further investigations.

Differential expression of lymphocyte antigen 6 complex, locus E in human epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer (1). We performed discovery of genes associated with epithelial ovarian cancer and of the high-grade serous ovarian cancer (HGSC) subtype, using published microarray data (2, 3) to compare global gene expression profiles of normal ovary or fallopian tube with that of primary tumors from women diagnosed with epithelial ovarian cancer or HGSC. We identified the gene encoding lymphocyte antigen 6 complex, locus E, LY6E, as among the genes whose expression was most different in epithelial ovarian cancer as compared to the normal fallopian tube. LY6E expression was significantly higher in high-grade serous ovarian tumors relative to normal fallopian tube. LY6E expression correlated with progression-free survival in patients with ovarian cancer. These data indicate that expression of LY6E is perturbed in epithelial ovarian cancers broadly and in ovarian cancers of the HGSC subtype. LY6E may be relevant to pathways underlying ovarian cancer initiation (transformation) or progression.

Genetic Variation and Population Differentiation in the Bovine Lymphocyte Antigen DRB3.2 Locus of South African Nguni Crossbred Cattle

The bovine lymphocyte antigen (BoLA-DRB3) gene is an important region that codes for glycoproteins responsible for the initiation of an immune response. BoLA-DRB3 alleles have been demonstrated to be associated with disease resistance/tolerance. Therefore, great genetic diversity is correlated with better adaptation, fitness, and robustness. The current study was conducted to assess the population genetic structure of the BoLA-DRB3 gene in Nguni crossbred cattle using polymerase chain reaction-sequence based typing (PCR-SBT). High genetic diversity was detected, with 30 alleles, 11 of which are novel to the study. Alleles DRB3*0201, DRB3*0701, DRB*0901, and DRB*1601 were present in all populations and accounted for nearly around 50% of all observed alleles. A mean genetic diversity (HE) of 0.93 was detected. The high overall genetic diversity is possibly associated with pathogen-assisted selection and heterozygote advantage. Such high diversity might explain the hardiness of the Nguni crossbred cattle to the Southern African region. Low population genetic structure was identified (FST = 0.01), suggesting possible gene flow between populations and retention of similar alleles. The study was undertaken to bridge the dearth of such studies in South African breeds and it is imperative for effective sustainability of indigenous breeds and the implementation of effective breeding strategies.

Cytotoxic T-Lymphocyte Antigen-4 in Colorectal Cancer: Another Therapeutic Side of Capecitabine

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory immune checkpoint that can be expressed in tumor-infiltrating lymphocytes and colorectal cancer (CRC) cells. This immune checkpoint can attenuate anti-tumoral immune responses and facilitate tumor growth and metastasis. Although capecitabine is an effective chemotherapeutic agent for treating CRC, its effect on the tumoral CTLA-4 expression remains unclear. In the current research, we applied the GSE110224 and GSE25070 datasets to characterize CTLA-4 expression in CRC patients. Then, we analyzed CTLA-4 expression in CRC samples, HT-29, HCT-166, and SW480 cell lines using real-time PCR. Our bioinformatic results have highlighted the overexpression of CTLA-4 in the CRC tissues compared to the adjacent non-tumoral tissues. Our in vitro studies have indicated that SW480 cells can substantially overexpress CTLA-4 compared to HT-29 and HCT 116 cells. In addition, capecitabine can remarkably downregulate the expression of CTLA-4 in SW480 cells. Collectively, capecitabine can inhibit the expression of CTLA-4 in CRC cells and might bridge the immunotherapy approaches with chemotherapy.