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Innate Immunity: Mechanisms and Modulation | EK39


EK39-eposter-baeyens-audrey - Monocyte-derived S1P in the lymph node regulates immune responses


Apr 12, 2021 12:00am ‐ Apr 12, 2021 12:00am

Description

Monocyte-derived S1P in the lymph node regulates immune responses 1: Audrey Baeyens: Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, NY, USA. 2: Sabrina Bracero: Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, NY, USA.; Present address: Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, USA; 3: Venkata S. Chaluvadi: Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, NY, USA.; Present address: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 4: Alireza Khodadadi-Jamayran: Office of Collaborative Science, New York University Langone Medical Center, New York, NY, USA 5: Michael Cammer: Office of Collaborative Science, New York University Langone Medical Center, New York, NY, USA 6: Susan R. Schwab: Skirball Institute of Biomolecular Medicine, New York University Langone Medical Center, New York, NY, USA. The lipid chemoattractant sphingosine 1-phosphate (S1P) guides cells out of tissues, where the concentration of S1P is relatively low, into circulatory fluids, where the concentration of S1P is high. For example, S1P directs the exit of T cells from lymph nodes, where T cells are initially activated, into lymph, from which T cells reach the blood and ultimately inflamed tissues. T cells follow S1P gradients primarily using S1P receptor 1. Recent studies have described how S1P gradients are established at steady state, but little is known about the distribution of S1P in disease or about how changing levels of S1P may affect immune responses. Here we show that the concentration of S1P increases in lymph nodes during an immune response. We found that haematopoietic cells, including inflammatory monocytes, were an important source of this S1P, which was an unexpected finding as endothelial cells provide S1P to lymph. Inflammatory monocytes required the early activation marker CD69 to supply this S1P, in part because the expression of CD69 was associated with reduced levels of S1pr5 (which encodes S1P receptor 5). CD69 acted as a ‘stand-your-ground’ signal, keeping immune cells at a site of inflammation by regulating both the receptors and the gradients of S1P. Finally, increased levels of S1P prolonged the residence time of T cells in the lymph nodes and exacerbated the severity of experimental autoimmune encephalomyelitis in mice. This finding suggests that residence time in the lymph nodes might regulate the differentiation of T cells, and points to new uses of drugs that target S1P signalling.

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