TY - GEN A1 - Rodriguez-Sillke, Yasmina A1 - Steinhoff, U. A1 - Bojarski, Christian A1 - Lissner, Donata A1 - Schumann, Michael A1 - Branchi, F. A1 - Siegmund, Britta A1 - Glauben, Rainer T1 - Deep immune profiling of human Peyer´s Patches in patients of inflammatory bowel diseases T2 - European journal of immunology Y1 - 2019 U6 - https://doi.org/10.1002/eji.201970300 SN - 0014-2980 SN - 1521-4141 VL - 49 SP - 203 EP - 204 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Wu, Hao A1 - Han, Yijie A1 - Rodriguez Sillke, Yasmina A1 - Deng, Hongzhang A1 - Siddiqui, Sophiya A1 - Treese, Christoph A1 - Schmidt, Franziska A1 - Friedrich, Marie A1 - Keye, Jacqueline A1 - Wan, Jiajia A1 - Qin, Yue A1 - Kühl, Anja A. A1 - Qin, Zhihai A1 - Siegmund, Britta A1 - Glauben, Rainer T1 - Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages JF - EMBO molecular medicine N2 - Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level. KW - cancer immunotherapy KW - lipid droplets KW - lipid metabolism KW - tumor microenvironment KW - tumor-associated macrophage Y1 - 2019 U6 - https://doi.org/10.15252/emmm.201910698 SN - 1757-4676 SN - 1757-4684 VL - 11 IS - 11 PB - Wiley CY - Hoboken ER - TY - THES A1 - Rodriguez-Sillke, Yasmina T1 - Der Einfluss von Nahrungsmittelantigenen auf die mukosale sowie periphere Homöostase und Entzündung bei chronisch entzündlichen Darmerkrankungen Y1 - 2021 ER - TY - GEN A1 - Rodríguez Sillke, Yasmina A1 - Schumann, Michael A1 - Lissner, Donata A1 - Branchi, Frederica A1 - Glauben, Rainer A1 - Siegmund, Britta T1 - Small intestinal inflammation but not colitis drives pro-inflammatory nutritional antigen-specific T-cell response T2 - Journal of Crohn's and Colitis N2 - Background: Inflammatory bowel disease (IBD) represents a dysregulation of the mucosal immune system. The pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC) is linked to the loss of intestinal tolerance and barrier function. The healthy mucosal immune system has previously been shown to be inert against food antigens. Since the small intestine is the main contact surface for antigens and therefore the immunological response, the present study served to analyse food-antigen-specific T cells in the peripheral blood of IBD patients. Methods: Peripheral blood mononuclear cells of CD, with an affected small intestine, and UC (colitis) patients, either active or in remission, were stimulated with the following food antigens: gluten, soybean, peanut and ovalbumin. Healthy controls and celiac disease patients were included as controls. Antigen-activated CD4+ T cells in the peripheral blood were analysed by a magnetic enrichment of CD154+ effector T cells and a cytometric antigen-reactive T-cell analysis (‘ARTE’ technology) followed by characterisation of the ef- fector response. Results: The effector T-cell response of antigen-specific T cells were compared between CD with small intestinal inflammation and UC where inflammation was restricted to the colon. Among all tested food antigens, the highest frequency of antigen-specific T cells (CD4+CD154+) was found for gluten. Celiac disease patients were included as control, since gluten has been identified as the disease- causing antigen. The highest frequency of gluten antigen-specific T cells was revealed in active CD when compared with UC, celiac disease on a gluten-free diet (GFD) and healthy controls. Ovalbuminspecific T cells were almost undetectable, whereas the reaction to soybean and peanut was slightly higher. But again, the strong- est reaction was observed in CD with small intestinal involvement compared with UC. Remarkably, in celiac disease on a GFD only antigen-specific cells for gluten were detected. These gluten-specific T cells were characterised by up-regulation of the pro-inflammatory cytokines IFN-γ, IL-17A and TNF-α. IFN-g was exclusively elevated in CD patients with active disease. Gluten-specific T-cells expressing IL-17A were increased in all IBD patients. Furthermore, T cells of CD patients, independent of disease activity, revealed a high expression of the pro-inflammatory cytokine TNF-α. Conclusion: The ‘ARTE’-technique allows to analyse and quantify food antigen specific T cells in the peripheral blood of IBD patients indicating a potential therapeutic insight. These data provide evidence that small intestinal inflammation in CD is key for the development of a systemic pro-inflammatory effector T-cell response driven by food antigens. Y1 - 2020 U6 - https://doi.org/10.1093/ecco-jcc/jjz203.172 SN - 1873-9946 SN - 1876-4479 VL - 14 SP - S154 EP - S155 PB - Oxford Univ. Press CY - Oxford ER -