PMID- 25803042 OWN - NLM STAT- MEDLINE DCOM- 20160407 LR - 20240326 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - T-cell activation and early gene response in dogs. PG - e0121169 LID - 10.1371/journal.pone.0121169 [doi] LID - e0121169 AB - T-cells play a crucial role in canine immunoregulation and defence against invading pathogens. Proliferation is fundamental to T-cell differentiation, homeostasis and immune response. Initiation of proliferation following receptor mediated stimuli requires a temporally programmed gene response that can be identified as immediate-early, mid- and late phases. The immediate-early response genes in T-cell activation engage the cell cycle machinery and promote subsequent gene activation events. Genes involved in this immediate-early response in dogs are yet to be identified. The present study was undertaken to characterise the early T-cell gene response in dogs to improve understanding of the genetic mechanisms regulating immune function. Gene expression profiles were characterised using canine gene expression microarrays and quantitative reverse transcription PCR (qRT-PCR), and paired samples from eleven dogs. Significant functional annotation clusters were identified following stimulation with phytohemagluttinin (PHA) (5mug/ml), including the Toll-like receptor signaling pathway and phosphorylation pathways. Using strict statistical criteria, 13 individual genes were found to be differentially expressed, nine of which have ontologies that relate to proliferation and cell cycle control. These included, prostaglandin-endoperoxide synthase 2 (PTGS2/COX2), early growth response 1 (EGR1), growth arrest and DNA damage-inducible gene (GADD45B), phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), V-FOS FBJ murine osteosarcoma viral oncogene homolog (FOS), early growth response 2 (EGR2), hemogen (HEMGN), polo-like kinase 2 (PLK2) and polo-like kinase 3 (PLK3). Differential gene expression was re-examined using qRT-PCR, which confirmed that EGR1, EGR2, PMAIP1, PTGS2, FOS and GADD45B were significantly upregulated in stimulated cells and ALAS2 downregulated. PTGS2 and EGR1 showed the highest levels of response in these dogs. Both of these genes are involved in cell cycle regulation. This study provides a comprehensive analysis of the early T-cell gene response to activation in dogs. FAU - Mortlock, Sally-Anne AU - Mortlock SA AD - Faculty of Veterinary Science, The University of Sydney, NSW 2006, Australia. FAU - Wei, Jerry AU - Wei J AD - Faculty of Veterinary Science, The University of Sydney, NSW 2006, Australia; Sydney Medical School, The University of Sydney, NSW 2006, Australia. FAU - Williamson, Peter AU - Williamson P AD - Faculty of Veterinary Science, The University of Sydney, NSW 2006, Australia. LA - eng SI - GEO/GSE65158 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150324 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Animals MH - Cluster Analysis MH - Dogs/*genetics/*immunology MH - Female MH - *Genes, Immediate-Early MH - Lymphocyte Activation/genetics/immunology MH - Male MH - Real-Time Polymerase Chain Reaction MH - T-Lymphocytes/*immunology/*physiology MH - Transcriptome PMC - PMC4372360 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/03/25 06:00 MHDA- 2016/04/08 06:00 PMCR- 2015/03/24 CRDT- 2015/03/25 06:00 PHST- 2014/11/06 00:00 [received] PHST- 2015/01/28 00:00 [accepted] PHST- 2015/03/25 06:00 [entrez] PHST- 2015/03/25 06:00 [pubmed] PHST- 2016/04/08 06:00 [medline] PHST- 2015/03/24 00:00 [pmc-release] AID - PONE-D-14-50073 [pii] AID - 10.1371/journal.pone.0121169 [doi] PST - epublish SO - PLoS One. 2015 Mar 24;10(3):e0121169. doi: 10.1371/journal.pone.0121169. eCollection 2015.