The Human Interleukin-4 Treated Macrophage and Epithelial Wound Repair

Jayme, Timothy

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