Stromal cells of the mouse spleen

The composition and function of stromal cells in the white pulp of the spleen resemble to a large extent the situation in other secondary lymphoid organs such as lymph nodes. The stromal cells play an important role in the support and guidance of lymphocytes and myeloid cells in the T and B cell zones of the spleen. Major differences of the spleen are found in the way cells enter the white pulp and the composition of stromal cells in the red pulp

Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan Sulfate and Determines Adaptive Immunity Magnitude

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Development of a Retinal-Based Probe for the Profiling of Retinaldehyde Dehydrogenases in Cancer Cells

Retinaldehyde dehydrogenases belong to a superfamily of enzymes that regulate cell differentiation and are responsible for detoxification of anticancer drugs. Chemical tools and methods are of great utility to visualize and quantify aldehyde dehydrogenase (ALDH) activity in health and disease. Here, we present the discovery of a first-in-class chemical probe based on retinal, the endogenous substrate of retinal ALDHs. We unveil the utility of this probe in quantitating ALDH isozyme activity in a panel of cancer cells via both fluorescence and chemical proteomic approaches. We demonstrate that our probe is superior to the widely used ALDEFLUOR assay to explain the ability of breast cancer (stem) cells to produce all-trans retinoic acid. Furthermore, our probe revealed the cellular selectivity profile of an advanced ALDH1A1 inhibitor, thereby prompting us to investigate the nature of its cytotoxicity. Our results showcase the application of substrate-based probes in interrogating pathologically relevant enzyme activities. They also highlight the general power of chemical proteomics in driving the discovery of new biological insights and its utility to guide drug discovery efforts.Bio-organic SynthesisMolecular Physiolog

Role of chemokines in the development of secondary and tertiary lymphoid tissues.

Organogenesis of lymph nodes and Peyer's patches is initiated during embryonic development and depends on the correct expression of a wide variety of molecules. Essential for this process is the paracrine triggering of stromal cells by CD45+CD4+CD3- cells. Hereto CD45+CD4+CD3- cells and stromal cells need to be spatially positioned in close proximity to each other. Expression of adhesion molecules and chemokines is thought to be essential for this process. During adult life, similar processes might also be at the basis of development of organized tertiary lymphoid structures often seen in inflammatory lesions