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Secondary lymphoid organs such as lymph nodes (LNs) and
Peyer’s patches (PPs) sample antigens from the body’s inner and outer surfaces and mediate optimal interaction of immune cells. These functions rely on the presence of specialized microenvironments that are built and maintained by fibroblastic reticular cells (FRCs). In addition to their scaffold-building function, FRCs impact on inducing
and shaping innate and adaptive immune responses. However, we do not know the embryonic origin of these important cells and the molecular mechanisms underlying FRC differentiation in LNs or PPs. Our laboratory has generated the appropriate lineage-tracing and fate-mapping approach to address these questions. Accordingly,
the work program of this project has been designed on the basis of two main hypotheses: (i) LN and PP FRCs originate from an organ-specific pluripotent embryonic precursor cell, and (ii) committed embryonic LN FRC progenitors descend from fat pad fibroblasts.

Only in recent years, has the importance of secondary lymphoid organ stromal cells for induction and regulation of immune responsiveness been appreciated. The field is now rapidly moving forward exploring functions and exploiting the potential of these cells as therapeutic targets in autoimmune diseases, cancer and infection. We anticipate that defining the origin of fibroblastic stromal cells and elaborating the mechanisms that govern subset differentiation in LNs and PPs will provide critical knowledge to further elaborate diagnostic and therapeutic avenues for various diseases.