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dc.contributor.author
Hunter, Morgan Campbell
dc.contributor.supervisor
Halin Winter, Cornelia
dc.contributor.supervisor
Neri, Dario
dc.date.accessioned
2019-06-11T12:49:58Z
dc.date.available
2019-06-11T12:12:18Z
dc.date.available
2019-06-11T12:49:58Z
dc.date.issued
2019
dc.identifier.uri
http://hdl.handle.net/20.500.11850/346769
dc.identifier.doi
10.3929/ethz-b-000346769
dc.description.abstract
Afferent lymphatic vessels mediate the transport of antigen and leukocytes to draining lymph nodes, thereby serving as immunologic communication highways between peripheral tissues and lymph nodes. The main cell types migrating via this route are antigen-presenting dendritic cells (DCs) and antigen-experienced T cells. While DC migration is important for maintenance of tolerance and induction of adaptive immunity in draining lymph nodes, T cell migration through afferent lymphatics is thought to contribute to immunesurveillance. DC migration from the skin to lymph nodes has previously been shown to occur in a step-wise manner. Herein we investigated whether T cells displayed similar migratory steps, and furthermore, whether - similarly to lymph nodes - adaptive DC-T cell interactions occurred within afferent lymphatics. Performing intravital microscopy in murine ear skin we showed that, similarly to DCs, T cells spent several hours actively crawling within initial lymphatic capillaries and were only passively transported to the draining lymph node once they reached contracting collecting vessels segments (Chapter 4). We further showed that inflammation-induced upregulation of ICAM-1 on lymphatic endothelium supported T cell exit from inflamed skin. These findings for the first time detail the cellular steps in T cell migration through afferent lymphatics, identify a novel molecule involved in this migration, and support the findings of others that an inflammation-induced mechanism facilitates enhanced exit of leukocytes from the skin. We also showed that intralymphatic T cells frequently interacted with DCs inside lymphatic capillaries (Chapter 5). T cell recognition of cognate antigen on DCs prolonged intralymphatic interactions, reduced the speed of intralymphatic DC crawling, but did not delay overall DC migration to lymph nodes. We further showed that regulatory T cells interacted with DCs inside lymphatic capillaries and that these interactions occurred more frequently inside lymphatics than in surrounding tissue (Chapter 6). While further consequences of these interactions still need to be explored, these findings suggest that afferent lymphatic vessels serve as more than a mere transport conduit to the lymph node, but also as a unique compartment in which adaptive immune interaction and modulation occur. Overall, these findings significantly extend the current perspective on the role of afferent lymphatics in the immune response.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
ETH Zurich
en_US
dc.subject
Immunology
en_US
dc.subject
Dendritic cell migration
en_US
dc.subject
T cell migration
en_US
dc.subject
immune interactions
en_US
dc.title
Leukocyte migration through afferent lymphatic vessel: molecular mechanisms and cellular interactions
en_US
dc.type
Doctoral Thesis
dc.date.published
2019-06-11
ethz.size
165 p.
en_US
ethz.code.ddc
DDC - DDC::6 - Technology, medicine and applied sciences::610 - Medical sciences, medicine
ethz.code.ddc
DDC - DDC::5 - Science::570 - Life sciences
ethz.identifier.diss
25776
en_US
ethz.publication.place
Zurich
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03816 - Halin Winter, Cornelia / Halin Winter, Cornelia
en_US
ethz.date.deposited
2019-06-11T12:12:25Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Embargoed
en_US
ethz.date.embargoend
2021-06-11
ethz.rosetta.installDate
2019-06-11T12:50:18Z
ethz.rosetta.lastUpdated
2019-06-11T12:50:18Z
ethz.rosetta.versionExported
true
ethz.COinS
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