Ana-Maria Lennon-Duménil
"Cell-Shape Sensing in Dendritic Cells"
Lecture
Motile cells such as immune cells experience large deformation events that result from the physical constraints they encounter while migrating within tissues or circulating between organs. It has become increasingly clear that these cells can survive and adapt to these changes in cell shape using dedicated shape sensing pathways. However, how shape sensing impacts their function and fate remains largely unknown. Here, we identify a shape sensing mechanism that couples cell motility to expression of CCR7, the chemokine receptor that guides immune cells to lymph nodes. We found that this mechanism is controlled by the lipid metabolism enzyme cPLA2, requires an intact nuclear envelop and exhibits an exquisitely sensitive activation threshold tuned by ARP2/3 and its inhibitor Arpin. We further show that shape sensing through the ARP2/3-cPLA2 axis controls Ikkb-NFkB-dependent transcriptional reprogramming of dendritic cells, which instructs them to migrate to lymph nodes in an immunoregulatory state compatible with their homeostatic tolerogenic function. These results highlight that the cell shape changes experienced by motile cells evolving within the complex environment of tissues can dictate their behavior and fate.
Biography
Ana-Maria Lennon-Duménil graduated as a biologist at the University of Chile in 1993. She did her PhD at the Pasteur Institute in Paris and her postdoc in the lab of Hidde Ploegh at Harvard Medical School. Since 2004, she has been a team leader in the Department of Immunity and Cancer at the Curie Institute in Paris. Her work has focused on combining immunology with other disciplines such as genetics (PhD stage), biochemistry/organic chemistry (postdoctoral stage), and cell biology/ biophysics (as group leader) to address fundamental questions on how immune cells work. Together with biophysicist Matthieu Piel (Curie Institute) and theoretician Raphaël Voituriez (Pierre and Marie Curie University), she has built a consortium aimed at studying dendritic cell migration in confinement using a quantitative multidisciplinary approach. Their work has opened a yet unexplored research line on how the function of immune cells is coordinated with their migratory capacity and on the molecular players involved in such coordination. In 2018, AnaMaria was nominated as a member of the European Molecular Biology Organization (EMBO) and received the national research award from the French National Institute for Health and Medical Research (Inserm).
https://institut-curie.org/personne/ana-maria-lennon
https://institut-curie.org/team/lennon
15 Aug 2023