Related Experiment Video
Updated: Mar 26, 2026
Visualization of IL-22-expressing Lymphocytes Using Reporter Mice
Published on: January 25, 2017
Variations in IL-23 and IL-25 receptor gene structure, sequence and expression associated with the two disease forms
Louise Nicol1, Anton Gossner2, Craig Watkins3
1The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. louise_nicol89@hotmail.co.uk.
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.
Insights
This study reveals distinct immune responses in sheep paratuberculosis, with specific interleukin receptor variants correlating with disease severity. Understanding these molecular differences is key to developing targeted treatments for this debilitating disease.
Area of Science:
- Veterinary immunology
- Molecular pathology
- Sheep infectious diseases
Background:
- Paucibacillary and multibacillary paratuberculosis exhibit distinct immunopathologies involving T cells and macrophages.
- Interleukin-23 (IL-23) and IL-25 signaling pathways, mediated by receptors IL-23R/IL-12RB1 and IL-17RA/IL-17RB, are crucial in disease development.
- Gene variations in these pathways are linked to human inflammatory conditions like tuberculosis, leprosy, and Crohn's disease.
Purpose of the Study:
- To investigate the expression patterns of sheep interleukin receptor variants in paratuberculosis.
- To correlate specific receptor variant expression with paucibacillary and multibacillary forms of the disease.
Main Methods:
- Sequencing identified multiple transcript variants for sheep IL23R, IL12RB1, and IL17RB, and a single IL17RA transcript.
- Quantitative reverse transcription PCR (RT-qPCR) assays were developed for all identified variants.
- Gene expression was compared in the ileo-caecal lymph node of infected and uninfected sheep.
Main Results:
- The IL12RB1v3 variant, lacking a receptor activation motif, was significantly increased in multibacillary paratuberculosis, potentially promoting Th2 responses.
- Full-length IL17RB was also significantly increased in multibacillary pathology, possibly contributing to Th2 polarization.
- IL17RA expression was significantly elevated in paucibacillary disease, suggesting a role for Th17 cells alongside Th1 cells.
Conclusions:
- Differential expression of specific interleukin receptor variants is associated with distinct paratuberculosis pathologies in sheep.
- The findings highlight the complex role of IL-23 and IL-17 signaling in disease pathogenesis.
- Further research into these pathways could inform novel therapeutic strategies for paratuberculosis.
