Most cited article - PubMed ID 29719531
Characterization of Chicken Tumor Necrosis Factor-α, a Long Missed Cytokine in Birds
BACKGROUND: Interferon regulatory factors (IRFs) are a family of transcription factors with important functions in immunity. The genomes of most vertebrates encode ten IRF genes. IRF3 and IRF9 have key roles in interferon (IFN) induction and signaling. Most of our knowledge about the IFN pathways originates from the study of the mammalian IFN system, and the description of the corresponding avian components is not as complete. Both IRF3 and IRF9 were considered missing from the chicken genome and from the genomes of other avian species. RESULTS: Here we describe multiple avian IRF3 and IRF9 genes, all with difficult GC-rich sequence context that prevented their earlier characterization. IRF3 orthologs are narrowly distributed and are present in the avian infraclass Palaeognathae. In contrast, IRF9 orthologs were found in most avian species, with the exception of the order Galliformes. In about half of the avian orders, IRF9 was located in noncanonical chromosomal positions, indicating past translocations. Phylogenetic analysis confirmed the correct orthology of all newly described IRFs. We further performed experiments using duck IRF9, confirming its role in the IFN pathway. IRF9 knockout in duck fibroblasts decreases the induction of IFN-stimulated genes (ISGs). Full induction of ISGs in duck cells requires both an intact IRF9 and a canonical IFN-stimulated response element. Lastly, intact IRF9 is needed for IFN-mediated protection of duck cells against the vesicular stomatitis virus-induced cytopathicity. CONCLUSIONS: The identification of avian IRFs fills an important gap in our understanding of avian immunology and brings new questions related to the evolution of the IRF family.
- Keywords
- Avian genome, Gene loss, Interferon regulatory factors, Interferon signaling,
- MeSH
- Phylogeny MeSH
- Interferon Regulatory Factors * genetics metabolism MeSH
- Interferon Regulatory Factor-3 * genetics metabolism MeSH
- Interferon-Stimulated Gene Factor 3, gamma Subunit * genetics metabolism MeSH
- Ducks genetics MeSH
- Chickens genetics MeSH
- Avian Proteins * genetics metabolism MeSH
- Birds * genetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Interferon Regulatory Factors * MeSH
- Interferon Regulatory Factor-3 * MeSH
- Interferon-Stimulated Gene Factor 3, gamma Subunit * MeSH
- Avian Proteins * MeSH
Linker for activation of T cells (LAT) plays a key role in T-cell antigenic signaling in mammals. Accordingly, LAT orthologues were identified in the majority of vertebrates. However, LAT orthologues were not identified in most birds. In this study, we show that LAT gene is present in genomes of multiple extant birds. It was not properly assembled previously because of its GC-rich content. LAT expression is enriched in lymphoid organs in chicken. The analysis of the coding sequences revealed a strong conservation of key signaling motifs in LAT between chicken and human. Overall, our data indicate that mammalian and avian LAT genes are functional homologues with a common role in T-cell signaling.
- MeSH
- Adaptor Proteins, Signal Transducing * genetics MeSH
- Phosphoproteins metabolism MeSH
- Genome MeSH
- Chickens genetics metabolism MeSH
- Humans MeSH
- Membrane Proteins * genetics MeSH
- Mammals genetics MeSH
- T-Lymphocytes metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adaptor Proteins, Signal Transducing * MeSH
- Phosphoproteins MeSH
- Membrane Proteins * MeSH
The Czech Republic, a part of the former Czechoslovakia, has been at the forefront of several research directions in virology, genetics and physiology [...].
- MeSH
- Virology * MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Editorial MeSH
- Geographicals
- Czech Republic MeSH
In mammals, leptin and tumor-necrosis factor (TNF) are prominent interacting adipokines mediating appetite control and insulin sensitivity. While TNF pleiotropically functions in immune defense and cell survival, leptin is largely confined to signaling energy stores in adipocytes. Knowledge about the function of avian leptin and TNF is limited and they are absent or lowly expressed in adipose, respectively. Employing radiation-hybrid mapping and FISH-TSA, we mapped TNF and its syntenic genes to chicken chromosome 16 within the major histocompatibility complex (MHC) region. This mapping position suggests that avian TNF has a role in regulating immune response. To test its possible interaction with leptin within the immune system and beyond, we compared the transcription patterns of TNF, leptin and their cognate receptors obtained by meta-analysis of GenBank RNA-seq data. While expression of leptin and its receptor (LEPR) were detected in the brain and digestive tract, TNF and its receptor mRNAs were primarily found in viral-infected and LPS-treated leukocytes. We confirmed leptin expression in the duodenum by immunohistochemistry staining. Altogether, we suggest that whereas leptin and TNF interact as adipokines in mammals, in birds, they have distinct roles. Thus, the interaction between leptin and TNF may be unique to mammals.
- Keywords
- FISH-TSA, TNF, chicken, digestive tract, duodenum, immune system, leptin, radiation-hybrid mapping,
- MeSH
- Cell Line MeSH
- Duodenum metabolism MeSH
- Chickens genetics metabolism MeSH
- Leptin genetics metabolism MeSH
- Receptors, Leptin metabolism MeSH
- Chromosome Mapping * MeSH
- Radiation Hybrid Mapping MeSH
- RNA, Messenger genetics metabolism MeSH
- Metaphase genetics MeSH
- Receptors, Tumor Necrosis Factor genetics metabolism MeSH
- Gene Expression Regulation * MeSH
- Mammals genetics MeSH
- Signal Transduction * MeSH
- Synteny genetics MeSH
- Tumor Necrosis Factor-alpha genetics metabolism MeSH
- Digestion * MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Leptin MeSH
- Receptors, Leptin MeSH
- RNA, Messenger MeSH
- Receptors, Tumor Necrosis Factor MeSH
- Tumor Necrosis Factor-alpha MeSH
It has now been more than two years since we said our last goodbye to Jan Svoboda (14 [...].
