Gradients of the signaling lipid S1P in lymph nodes position natural killer cells and regulate their interferon-γ response.

Nat Immunol. 2017 Jan;18(1):15-25. doi: 10.1038/ni.3619. | PubMed

Victoria Fang¹, V Sai Chaluvadi¹, Willy D Ramos-Perez¹, Alejandra Mendoza¹, Audrey Baeyens¹, Richard Rivera², Jerold Chun², Michael Cammer³, Susan R Schwab¹

1. Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.
2. Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA.
3. Microscopy Core, Office of Collaborative Science, New York University Langone Medical Center, New York, New York, USA.

Abstract

The lymph node periphery is an important site for many immunological functions, from pathogen containment to the differentiation of helper T cells, yet the cues that position cells in this region are largely undefined. Here, through the use of a reporter for the signaling lipid S1P (sphingosine 1-phosphate), we found that cells sensed higher concentrations of S1P in the medullary cords than in the T cell zone and that the S1P transporter SPNS2 on lymphatic endothelial cells generated this gradient. Natural killer (NK) cells are located at the periphery of the lymph node, predominantly in the medulla, and we found that expression of SPNS2, expression of the S1P receptor S1PR5 on NK cells, and expression of the chemokine receptor CXCR4 were all required for NK cell localization during homeostasis and rapid production of interferon-γ by NK cells after challenge. Our findings elucidate the spatial cues for NK cell organization and reveal a previously unknown role for S1P in positioning cells within the medulla.

Presented By Victoria Fang