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Immune responses in the intestine are thought to be induced in the Peyer´s patches (PP) that contain specialized microfold cells that directly sample antigens from the intestinal lumen. In addition, numerous other lymphoid structures are present in the intestine that together harbour more immune cells than PP. Surprisingly, the function of these small sized structures is mostly unknown or controversially discussed in the literature.
We have previously established a method that allows the systematic analysis of large coherent areas of the intestinal wall by automated multi-colour immunofluorescence microscopy. When we applied this technique to systematically analyze small sized lymphoid structures in the murine intestine, we observed, that the current classification of different types of these aggregations is not suited to describe these structures properly. In consequence, we proposed to refer to these structures in their totality as “solitary intestinal lymphoid tissue” (SILT), thereby high lightening their dynamic and inter-convertible nature. The aim as this project is to further characterize the phenotype, organogenesis and function of SILT.
The functional analysis of SILT will be based on the generation of manipulated animals that do not have PP but process normal SILT, do have normal PP but do not have SILT or do have neither PP nor SILT. These animals will be analyzed for their ability to induce oral tolerance, as well as humeral and anti-viral immune responses. In addition we will transplant intestinal tubes of different genetically manipulated mice into wild type recipients. “Feeding” of the transplanted intestinal tubes will allow the characterization of immune responses initiated in a mutant organ in the context of a wild type animal.
Organogenesis of lymphoid organs is initiated by the interaction of mesenchymal stromal cells with “lymphoid tissue inducing cells” (LTIC). As organogenesis of SILT starts postnatally, this offers the unique chance to manipulate organogenesis at its endogenous time point. We could demonstrate that SILT fails to form in lymphotoxin mutants but can be induced by bone marrow transplantation. Next we will test LTIC isolated from different organs and time points for the potency to induce SILT formation.
In the context of a further phenotypic description of SILT in germ free animals and during re-colonization this work will have large influence on our current understanding of the intestinal immune system, especially in respect to its functional anatomy.
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