Provenance mapping of immune cells in the CSF

A12

The initial phases of immunopathology in the CNS in MS are dictated by the systemic immune compartment. However, it is unknown in which sites of the immune system specific properties of immune cells that later traffic to the CNS are imprinted. Here, we will use an in vivo labeling system to track immune cells from the inguinal (iLN) or mesenteric lymph nodes (mLN) to the CNS. By single cell analysis of the transcriptome and the TCR and BCR of lymphocytes re-isolated from the CNS and cerebrospinal fluid of EAE mice, we will correlate the mesenteric or inguinal provenance of these lymphocytes with their distinct properties in the CNS. We hypothesize that distinct transcriptional profiles are imprinted in T cells according to their site of priming in the peripheral immune compartment. This transcriptional program will later determine their positioning and functional specialization in the CNS. Based on this we ask::

    1. Specific properties are imprinted in in lymphocytes in distinct niches of the secondary lymphoid organs. Does this determine the functional phenotype of these lymphocytes in the CNS and in the CSF??
    2. In certain differential transcriptional modules in CNS T cells we find guidance molecules (integrins, chemokine receptors, cytoskeleton molecules, etc). Are they organized depending on whether they were primed in iLN or mLN?
    3. We will analyse known T helper cell subset modules: Are they differentially expressed in iLN derived vs mLN derived T cells recovered from the CNS?
    4. We will analyse tolerogenic or pathogenic modules. Are they differentially expressed in iLN vs mLN derived CNS T cells?

Single cell (sc) RNAseq analysis (10X) of
photoconverted T cells derived from the inguinal
vs mesenteric lmyph nodes: Inguinally (i) or
mesenterically (m).

 

 

 

 

Principal Investigators:

Univ.-Prof. Dr. med. Thomas Korn
Klinik für Neurologie
TU München
thomas.korn@tum.de

Priv.-Doz. Dr. med. Klaus Lehmann-Horn
Klinik für Neurologie
TU München
klaus.lehmann-horn@tum.de

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