title: Variations in IL-23 and IL-25 receptor gene structure, sequence and expression associated with the two disease forms of sheep paratuberculosis.
abstract: The immunopathology of paucibacillary and multibacillary sheep paratuberculosis is characterized by inflammatory T cell and macrophage responses respectively. IL-23 and IL-25 are key to the development of these responses by interaction with their complex receptors, IL-23R/IL-12RB1 and IL-17RA/IL-17RB. In humans, variations in structure, sequence and/or expression of these genes have been implicated in the different pathological forms of tuberculosis and leprosy, and in gastrointestinal inflammatory disorders such as Crohn's disease. Sequencing has identified multiple transcript variants of sheep IL23R, IL12RB1 and IL17RB and a single IL17RA transcript. RT-qPCR assays were developed for all the identified variants and used to compare expression in the ileo-caecal lymph node of sheep with paucibacillary or multibacillary paratuberculosis and uninfected animals. With IL-23 receptor, only the IL12RB1v3 variant, which lacks the receptor activation motif was differentially expressed and was significantly increased in multibacillary disease; this may contribute to high Th2 responses. Of the IL17RB variants only full length IL17RB was differentially expressed and was significantly increased in multibacillary pathology; which may also contribute to Th2 polarization. IL17RA expression was significantly increased in paucibacillary disease. The contrast between the IL17RA and IL17RB results may indicate that, in addition to Th1 cells, Th17 T cells are also involved in paucibacillary pathology.
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. louise_nicol89@hotmail.co.uk.
authors: Louise
authors: L
authors: Nicol
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. anton.gossner@ed.ac.uk.
authors: Anton
authors: A
authors: Gossner
authors: Moredun Research Institute, International Research Centre, Pentlands Science Park, Penicuik, Midlothian, EH26 0PZ, UK. craig.watkins@moredun.ac.uk.
authors: Craig
authors: C
authors: Watkins
authors: Moredun Research Institute, International Research Centre, Pentlands Science Park, Penicuik, Midlothian, EH26 0PZ, UK. francesca.chianini@moredun.ac.uk.
authors: Francesca
authors: F
authors: Chianini
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. bob.dalziel@ed.ac.uk.
authors: Robert
authors: R
authors: Dalziel
authors: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. john.hopkins@ed.ac.uk.
authors: John
authors: J
authors: Hopkins
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology; D008969:Molecular Sequence Data; D010283:Paratuberculosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018123:Receptors, Interleukin