The Human Interleukin-4 Treated Macrophage and Epithelial Wound Repair
| dc.contributor.advisor | McKay, Derek | |
| dc.contributor.advisor | Beck, Paul | |
| dc.contributor.author | Jayme, Timothy | |
| dc.contributor.committeemember | Jijon, Humberto | |
| dc.contributor.committeemember | Yates, Robin | |
| dc.contributor.committeemember | Hanington, Patrick | |
| dc.date | 2018-06 | |
| dc.date.accessioned | 2018-04-26T22:08:50Z | |
| dc.date.available | 2018-04-26T22:08:50Z | |
| dc.date.issued | 2018-04-17 | |
| dc.description.abstract | The murine interleukin-4 (IL-4) treated alternatively activated macrophage (M(IL4)) is known to have key roles in wound repair. Given that mucosal wound healing is the best indicator of long term remission for patients with inflammatory bowel disease (IBD), adoptive transfer of the M(IL4) in mice has been extensively studied as a therapeutic, and its beneficial outcome may be induced, in part, by M(IL4)s inducing wound healing. However, research has been extremely limited in translating these findings into human studies. Furthermore, helminth-derived soluble products can induce and enhance the M(IL4) phenotype in both mice and humans, however, its ability to enhance M(IL4) function is unknown. Therefore, my MSc research was designed to test the hypotheses that: 1) the human blood-derived M(IL4) can be an autologous cell immunotherapy for IBD by inducing mucosal wound repair; and, 2) in vitro treatment of M(IL4)s with an extract of the rat tapeworm, Hymenolepis diminuta (HdE), can enhance its capacity to wound repair. To my knowledge this is the first time that a human blood-derived M(IL4) (CD206highCCL18+CD14low) has been reported to promote colonic epithelial wound repair in an in vitro scratch assay: an ability dependent on TGF and prostaglandins. Furthermore, cryopreservation of human M(IL4)s, which could be an important process if used therapeutically, did not lose their ability to promote wound repair, although decreased M(IL4) markers were noted. Monocytes from patients with inactive Crohn’s disease or ulcerative colitis could be differentiated into M(IL4)s with the capacity to promote epithelial wound repair. Interestingly, M(IL4)s from patients with active Crohn’s disease and ulcerative colitis were more variable in their response to IL-4, and impaired M(IL4) activation (CD206lowCCL18+CD14low) correlated with an impaired ability to promote epithelial wound repair. This suggests that in vivo, M(IL4)s may have an important role in the resolution of inflammation by inducing mucosal wound repair in patients with active IBD. Finally, I could not find any direct evidence, in vitro, that HdE enhances the capacity of M(IL4)s to promote wound repair. Having defined the ability of the monocyte-derived M(IL4)s from healthy volunteers and patients with IBD to promote epithelial wound healing, my research lays the foundation for a more extensive investigation of the anti-inflammatory/pro-resolution activity of the human M(IL4), which could be used as an autologous transplant in a personalized medicine approach to IBD or other enteropathies. | en_US |
| dc.identifier.citation | Jayme, T. (2018). The Human Interleukin-4 Treated Macrophage and Epithelial Wound Repair (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/31846 | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/31846 | |
| dc.identifier.uri | http://hdl.handle.net/1880/106560 | |
| dc.language.iso | eng | |
| dc.publisher.faculty | Cumming School of Medicine | |
| dc.publisher.faculty | Graduate Studies | |
| dc.publisher.institution | University of Calgary | en |
| dc.publisher.place | Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | |
| dc.subject.classification | Education--Sciences | en_US |
| dc.title | The Human Interleukin-4 Treated Macrophage and Epithelial Wound Repair | |
| dc.type | master thesis | |
| thesis.degree.discipline | Gastrointestinal Sciences | |
| thesis.degree.grantor | University of Calgary | |
| thesis.degree.name | Master of Science (MSc) | |
| ucalgary.item.requestcopy | true |