Chronic (c) GvHD is immunologically distinct from acute (a) GvHD and its clinical presentation and symptoms are heterogeneous. Still, aGvHD predisposes for cGvHD. In cGvHD patients, isotype-switched antibodies are frequent as in various autoimmune diseases. Preclinical cGvHD models point towards disturbed germinal center (GC) formation containing GC-B cells and T-follicular helper (TFH) cells, but reduced T-follicular regulatory (TFR) cells.
Interestingly, TFH and TFR cells both express high levels of activated NFATc1 (alias NFAT2), a member of the transcription factor family NFAT.1,2 This raises the question how the standard GvHD therapy, which includes calcineurin (NFAT) inhibitors affects these different immune cell populations and compartments. Previously, we revealed that signaling of NFAT in T cells is crucial for aGvHD.3,4 Now we ask whether it is equally important for cGvHD. For this, T cells and / or Treg cells from NFAT-deficient mice can be transplanted in cGvHD models.
To explore the relevance of TFH cells in cGvHD in general, molecular control and function can be addressed according to our previous scRNA-seq analysis of human TFH cells. Besides flow cytometric and immunohistological analyses of TFH subsets from cGvHD patients, basic mechanisms can be evaluated in murine models of cGvHD by interference of CRISPR/Cas9-edited signaling pathways in TFH and TFR cells.3
Therefore, we are looking for a highly motivated and enthusiastic student with a good training in immunology as well as a solid background in molecular biology. Candidates with profound experience in pre-clinical mouse models will be considered first, whereas a minimum in mouse handling abilities is a pre-condition for the position.
Applications to [Email Address Removed] must contain a CV including records, a short motivation letter and the names of two references. Application deadline is September 15th, 2022.
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