|TRUONG, ANH - Chung-Ang University
|RENGARAJ, DEIVENDRAN - Chung-Ang University
|HONG, YEOJIN - Chung-Ang University
|HOANG, CONG - Chung-Ang University
|HONG, YEONG - Chung-Ang University
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2017
Publication Date: 5/2/2017
Publication URL: http://handle.nal.usda.gov/10113/5645091
Citation: Truong, A.D., Rengaraj, D., Hong, Y., Hoang, C.T., Lillehoj, H.S., Hong, Y.H. 2017. Analysis of JAK-STAT signaling pathway genes and their microRNA in the intestinal mucosa of genetically disparate chicken lines induced with necrotic enteritis. Veterinary Immunology and Immunopathology. 187:1–9. doi: 10.1016/j.vetimm.2017.03.001.
Interpretive Summary: Necrotic enteritis (NE) is an infectious disease caused by Clostridium perfringens, a commensal organism in the gastrointestinal track of chickens. There is an increasing interest to develop new non-drug treatment strategies against NE due to the elimination of antibiotics that have been traditionally used to control NE. In this report, ARS scientists and scientists in a South Korean university collaborated in studies intended to better understand host-pathogen interaction in order to find an alternative to antibiotic solution to prevent NE. Using large scale genomics tools to identify host genes that regulate host immune response to NE, many new host genes which influence host immune response to Clostridium perfringens have been identified. In particular, this paper reports for the first time that JAK-STAT pathway dysregulation results in the disruption of several signaling pathways involved in intestinal immune function in NE. The RNA-sequencing and bioinformatics analyses described in this study generated an abundant data that will guide future vaccine development against NE to decrease the use of antibiotics.
Technical Abstract: The JAK-STAT signaling pathway plays a key role in cytokine and growth factor activation and is involved in several cellular functions and diseases. The main objective of this study was to investigate and evaluate the expression of candidate JAK-STAT pathway genes and their regulators and interactors in the intestinal mucosal layer of two genetically disparate chicken lines [Marek's disease (MD)-resistant line 6.3 and MD-susceptible line 7.2] infected with necrotic enteritis (NE). Through RNA-sequencing, 116 JAK-STAT signaling pathway-related genes that were significantly differentially expressed in the intestinal mucosa of two lines were identified. About 15 JAK-STAT pathway genes were further verified by qRT-PCR, and the results were in agreement with our sequencing data. All the identified 116 genes were annotated using Gene Ontology and mapped to the KEGG chicken JAK-STAT signaling pathway. To the best of our knowledge, this is the first study to represent the transcriptional analysis of a large number of candidate genes, regulators, and potential interactors in the JAK-STAT pathway of the two chicken lines. Several key genes of the interactome, namely, STAT1/3/4, STAT5B, JAK1 -3, TYK2, AKT1/3, SOCS1 -5, PIAS1/2/4, PTPN6/11, and PIK3, were determined to be differentially expressed in the two lines. Moreover, we detected 68 known miRNAs targeting JAK-STAT pathway genes and differentially expressed in the two lines. The RNA-sequencing and bioinformatics analyses described in this study generated an abundant data that will guide future immunogenetic studies on JAK-STAT pathways associated with the function of two genetically disparate chicken lines with different NE disease susceptibility.