Naive T lymphocytes chemotax long distance to CCL21 but not to a source of bioactive S1P

Nicolas Garcia-Seyda; Solene Song; Valentine Seveau de Noray; Luc David-Broglio; Christoph Matti; Marc Artinger; Florian Dupuy; Martine Biarnes-Pelicot; Marie-Pierre Valignat; Daniel F Legler; Marc Bajénoff; Olivier Theodoly

doi:10.1016/j.isci.2023.107695

Naive T lymphocytes chemotax long distance to CCL21 but not to a source of bioactive S1P

iScience. 2023 Aug 19;26(10):107695. doi: 10.1016/j.isci.2023.107695. eCollection 2023 Oct 20.

Authors

Affiliations

¹ Aix Marseille University, Inserm, CNRS, Turing Center for Living Systems, LAI, Marseille, France.
² Aix Marseille University, Inserm, CNRS, CIML, Marseille, France.
³ Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Unterseestrasse 47, 8280 Kreuzlingen, Switzerland.
⁴ Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland.
⁵ Faculty of Biology, University of Konstanz, Universitätsstraße 10, 78464 Konstanz, Germany.
⁶ Theodor Kocher Institute, University of Bern, Freiestrasse 1, 3012 Bern, Switzerland.

Abstract

Naive T lymphocytes traffic through the organism in search for antigen, alternating between blood and secondary lymphoid organs. Lymphocyte homing to lymph nodes relies on CCL21 chemokine sensing by CCR7 receptors, while exit into efferent lymphatics relies on sphingolipid S1P sensing by S1PR1 receptors. While both molecules are claimed chemotactic, a quantitative analysis of naive T lymphocyte migration along defined gradients is missing. Here, we used a reductionist approach to study the real-time single-cell response of naive T lymphocytes to CCL21 and serum rich in bioactive S1P. Using microfluidic and micropatterning ad hoc tools, we show that CCL21 triggers stable polarization and long-range chemotaxis of cells, whereas S1P-rich serum triggers a transient polarization only and no significant displacement, potentially representing a brief transmigration step through exit portals. Our in vitro data thus suggest that naive T lymphocyte chemotax long distances to CCL21 but not toward a source of bioactive S1P.

Keywords: Cell biology; Immune response; Immunity.