Inhaltszusammenfassung

Multiple Sclerosis (MS) is an inflammatory disabling disease of the central nervous system (CNS) and is one of the most frequent causes of irreversible disability in young people. Both adaptive and innate immune cells infiltrate the CNS during MS and in its animal model experimental autoimmune encephalomyelitis (EAE). This thesis focuses on the impact of CNS-infiltrating and CNS-resident myeloid cells during neuroinflammation. Using deep mRNA sequencing (RNA-Seq), three distinct markers of al...Multiple Sclerosis (MS) is an inflammatory disabling disease of the central nervous system (CNS) and is one of the most frequent causes of irreversible disability in young people. Both adaptive and innate immune cells infiltrate the CNS during MS and in its animal model experimental autoimmune encephalomyelitis (EAE). This thesis focuses on the impact of CNS-infiltrating and CNS-resident myeloid cells during neuroinflammation. Using deep mRNA sequencing (RNA-Seq), three distinct markers of alternatively activated myeloid cells (aaMC), namely Ms4a8a, Ym1 and Arginase1, were here identified to be more highly expressed in the CNS during exacerbation of the disease compared to all other considered time points of disease development. This upregulation was detected in two different mouse strains despite strong genetic differences. aaMC exhibit beneficial properties during the disease and the upregulation of aaMC markers during the active state of the disease suggests the attempt of myeloid cells in the CNS to counteract disease progression. Among myeloid cells, microglia are CNS-resident and therefore particularly relevant regarding CNS inflammation. In the here presented work it was shown that microglia attempt to remove invading pathogenic T cells from the CNS tissue during the disease. Intravital two-photon imaging revealed that microglia intensely contacted pathogenic Th17 cells in inflammatory lesions. Strikingly, microglia were able to respond to CNS inflammation by engulfing invading T cells. This as of yet undefined engulfment process targeted fully viable T cells and was dependent on the strength of both T cell and microglial activation. While microglial activation significantly increased engulfment processes, inhibition of T cell activity decreased the engulfment of T cells, altogether clearly emphasizing the importance of engulfment processes in inflammation. The engulfment of living T cells in the CNS may therefore reflect a general defense mechanism of the CNS towards invading activated cells. In sum, both the upregulation of aaMC markers during the exacerbation of the disease as well as the engulfment of CNS-invading Th17 cells could serve as myeloid cell-mediated mechanisms to counteract neuroinflammation.» weiterlesen» einklappen

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DDC Sachgruppe:
Naturwissenschaften