Show simple item record

dc.contributor.supervisorKung, Sam (Immunology)en_US
dc.contributor.authorMahmood, Sajid
dc.date.accessioned2014-09-04T15:17:51Z
dc.date.available2014-09-04T15:17:51Z
dc.date.issued2012en_US
dc.date.issued2014en_US
dc.identifier.citationMahmood S, Kanwar N, Tran J, Zhang M-l, Kung SKP (2012) SHP-1 Phosphatase Is a Critical Regulator in Preventing Natural Killer Cell Self-Killing. PLoS ONE 7(8): e44244. doi:10.1371/journal.pone.0044244en_US
dc.identifier.citationMahmood, S., Nandagopal, S., Sow, I., Lin, F. and Kung, S. K. P. (2014), Microfluidic-based, live-cell analysis allows assessment of NK-cell migration in response to crosstalk with dendritic cells. Eur. J. Immunol.. doi: 10.1002/eji.201344244en_US
dc.identifier.urihttp://hdl.handle.net/1993/23963
dc.description.abstractNatural killer (NK) cells are innate lymphocytes with inherent ability to eliminate infected cells and produce several cytokines/chemokines. They express surface receptors to sense environment and interact with other immune cells including the Dendritic cells (DC). Reciprocally, DCs are also shown to activate NK-cells. NK/DC cross-talk is well-documented, yet the molecular interactions and the diverse NK-cell activities regulated by DC remain unclear. Several target proteins such as MHC-1, Qa-1 mediate NK-cell target recognition. One such antigen, Ocil/Clr-b functions as a cognate ligand of NKR-P1B/D, NK-inhibitory receptor. In first aim of my study, I documented that deficiency of Ocil/Clr-b expression not only augmented the sensitivity of DC towards NK-cell cytotoxicity but also regulated the development of mature NK-cells. Thus suggesting NKR-P1B/D:Ocil to be another receptor:ligand system, besides Ly49:MHC-1, that regulates NK-cell responsiveness. Src homology region 2-containing protein tyrosine phosphatase-1 (SHP-1) transmits inhibitory signals of the specific NK-inhibitory receptors, including NKRP-1B/D. SHP-1 silenced NK-cells showed unaffected target recognition towards prototypic target cells in this study. In addition, these cells also displayed an unexpected phenotype of self-killing in-vitro, thus implicated SHP-1 as an important regulator of some other unappreciated NK-cell functions. The data from my third study suggest that DCs are directly implicated in the induction of NK-cell migration. In summary, using a novel live-cell imaging microfluidic platform and conventional transwell migration assay this project established a clear molecular link between DC-derived soluble factors such as IP-10 and NK cell-chemokine receptor such as CXCR3. Previously, GM-CSF was shown as an inflammatory cytokine, involved in the development of DC as well as in mediating Th-1 immune responses. In this study I found that GM-CSF regulates NK-cell migration negatively. Lastly, the fourth aim of my thesis highlighted the critical role of immature-DC in the induction of maturation receptors (NK1.1 & Ly49) on differentiating NK-cells. I successfully established a multi-stage in-vitro NK-cell differentiation model and found that differentiating NK-cells required an active engagement with DCs, in addition to the soluble factors. I believe my PhD project findings would impact the existing knowledge to harness DC-based NK cell therapies in clinical settings.en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.publisherWiley Online Libraryen_US
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectNatural killer cellen_US
dc.subjectDendritic cellen_US
dc.titleDiverse regulation of natural killer cell functions by dendritic cellsen_US
dc.typeinfo:eu-repo/semantics/doctoralThesis
dc.typedoctoral thesisen_US
dc.degree.disciplineImmunologyen_US
dc.contributor.examiningcommitteeUzonna, Jude (Immunology) Soussi Gounni, Abdelilah (Immunology) Rempel, Julia (Immunology) Yao, Xiaojian (Medical Microbiology) Haeryfar, Mansour (University of Western Ontario)en_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.noteOctober 2014en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record