dc.contributor.advisor | Flügel, Alexander Prof. Dr. | |
dc.contributor.author | Cugota Canals, Roger | |
dc.date.accessioned | 2023-05-08T15:05:03Z | |
dc.date.available | 2023-05-11T00:50:12Z | |
dc.date.issued | 2023-05-08 | |
dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14660 | |
dc.identifier.uri | http://dx.doi.org/10.53846/goediss-9873 | |
dc.format.extent | XXX Seiten | de |
dc.language.iso | eng | de |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject.ddc | 570 | de |
dc.title | Crosstalk between the lung microenvironment and CNS autoimmunity | de |
dc.type | doctoralThesis | de |
dc.contributor.referee | Flügel, Alexander Prof. Dr. | |
dc.date.examination | 2022-05-13 | de |
dc.description.abstracteng | The contribution of the lung in shaping CNS autoimmunity is gaining relevance in the last years. Central
nervous system (CNS) reactive T cells can acquire in the lung the potential to invade the CNS in
experimental autoimmune encephalomyelitis, an animal model for Multiple sclerosis. Furthermore,
the lung microbiota by modulating the microglial phenotype can act on the effector phase of the CNS
autoreactive process and regulate the disease severity. Finally, the lung can also represent a trigger
site for CNS autoimmunity. Indeed, very low doses of CNS antigen delivered intra-trachea are sufficient
to trigger myelin-reactive T cells to induce EAE. As a repercussion of its main task of gas-exchange, the
lung represents the most extensive surface in contact with the outside environment and is the organ
with the highest level of oxygenation in the body. In this work, in order to identify pulmonary factors
that can potentially contribute to the efficiency of the lung in triggering autoimmunity, we
investigated if oxygen availability determines the function of CNS-reactive T cells in the context of CNS
autoimmunity.
In vitro, we could observe that an oxygen-deprived atmosphere impaired proliferation and effector
functions of myelin-reactive T cells stimulated with the cognate antigen. These functional changes
were associated with a global reprogramming of the transcriptional profile. The hypoxic stimulus,
rather that impairing, triggered an upregulation of numerous transcripts mainly involved in glucose
metabolism and cell signalling events. These transcriptional changes were clinical relevant. Indeed
myelin-reactive T cells stimulated in a hypoxic environment and retransferred in vivo proliferated less
than the normoxic counterpart did and induced a milder disease.
Taken together, our results indicated that the T cells are able to adapt their function to a broad range
of environmental oxygen conditions by rapidly switching their metabolism and transcriptional profile.
In the lung, the unique oxygen conditions favour T cells activation and proliferation and therefore
contribute to the capacity of the lung to trigger CNS autoimmunit | de |
dc.contributor.coReferee | Wienands, Jürgen Prof. Dr. | |
dc.contributor.thirdReferee | Reichardt, Holger Prof. Dr. | |
dc.contributor.thirdReferee | Stadelmann-Nessler, Christine Prof. Dr. | |
dc.contributor.thirdReferee | Ehrenreich, Hannelore Prof. Dr. Dr. | |
dc.contributor.thirdReferee | Weber, Martin Prof. Dr. | |
dc.subject.eng | Neuroimmunolgoy | de |
dc.subject.eng | Multiple sclerosis | de |
dc.subject.eng | Experimental Autoimmune Encephalomyelitis | de |
dc.identifier.urn | urn:nbn:de:gbv:7-ediss-14660-2 | |
dc.affiliation.institute | Biologische Fakultät für Biologie und Psychologie | de |
dc.subject.gokfull | Biologie (PPN619462639) | de |
dc.description.embargoed | 2023-05-11 | de |
dc.identifier.ppn | 1844928292 | |
dc.notes.confirmationsent | Confirmation sent 2023-05-08T15:15:01 | de |