lymph node; T cell activation; fibroblastic reticular cells; immune regulation
Dubey Lalit Kumar, Lebon Luc, Mosconi Ilaria, Yang Chen-Ying, Scandella Elke, Ludewig Burkhard, Luther Sanjiv A., Harris Nicola L. (2016), Lymphotoxin-Dependent B Cell-FRC Crosstalk Promotes De Novo Follicle Formation and Antibody Production following Intestinal Helminth Infection, in Cell Reports
, 15(7), 1527-1541.
Leignadier Julie, Favre Stephanie, Luther Sanjiv A., Luescher Immanuel F. (2015), CD8 engineered cytotoxic T cells reprogram melanoma tumor environment, in OncoImmunology
, 5(3), e1086861-e1086861.
Bernier-Latmani Jeremiah, Cisarovsky Christophe, Demir Cansaran Saygili, Bruand Marine, Jaquet Muriel, Davanture Suzel, Ragusa Simone, Siegert Stefanie, Dormond Olivier, Benedito Rui, Radtke Freddy, Luther Sanjiv A., Petrova Tatiana V. (2015), DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport, in Journal of Clinical Investigation
, 125(12), 4572-4586.
Barone Francesca, Nayar Saba, Campos Joana, Cloake Thomas, Withers David R., Toellner Kai-Michael, Zhang Yang, Fouser Lynette, Fisher Benjamin, Bowman Simon, Rangel-Moreno Javier, Garcia-Hernandez Maria de la Luz, Randall Troy D., Lucchesi Davide, Bombardieri Michele, Pitzalis Costantino, Luther Sanjiv A., Buckley Christopher D. (2015), IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs, in Proceedings of the National Academy of Sciences
, 112(35), 11024-11029.
Vanoaica Liviu, Richman Larry, Jaworski Maike, Darshan Deepak, Luther Sanjiv A., Kühn Lukas C. (2014), Conditional Deletion of Ferritin H in Mice Reduces B and T Lymphocyte Populations, in PLoS ONE
, 9(2), e89270-e89270.
Jaworski M., Marsland B. J., Gehrig J., Held W., Favre S., Luther S. A., Perroud M., Golshayan D., Gaide O., Thome M. (2014), Malt1 protease inactivation efficiently dampens immune responses but causes spontaneous autoimmunity, in The EMBO Journal
, 33(23), 2765-2781.
Fasnacht Nicolas, Huang Hsin-Ying, Koch Ute, Favre Stéphanie, Auderset Floriane, Chai Qian, Onder Lucas, Kallert Sandra, Pinschewer Daniel D, MacDonald H Robson, Tacchini-Cottier Fabienne, Ludewig Burkhard, Luther Sanjiv A, Radtke Freddy (2014), Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses., in The Journal of experimental medicine
, 211(11), 2265-79.
Yang Chen-Ying, Vogt Tobias K, Favre Stéphanie, Scarpellino Leonardo, Huang Hsin-Ying, Tacchini-Cottier Fabienne, Luther Sanjiv A (2014), Trapping of naive lymphocytes triggers rapid growth and remodeling of the fibroblast network in reactive murine lymph nodes., in Proceedings of the National Academy of Sciences of the United States of America
, 111(1), 109-18.
Ferrero Isabel, Koch Ute, Claudinot Stephanie, Favre Stéphanie, Radtke Freddy, Luther Sanjiv A., MacDonald H. R. (2013), DL4-mediated Notch signaling is required for the development of fetal αβ and γδ T cells, in European Journal of Immunology
, 43(11), 2845-2853.
Fiorini Emma, Ferrero Isabel, Poisson Caroline, Scarpellino Leonardo, Luther Sanjiv Andreas, MacDonald H. Robson (2013), Inducible gene expression in fetal thymic epithelium: A new BAC transgenic modelInducible Gene Expression in Fetal TECs, in genesis
, 51(10), 717-724.
Kania Gabriela, Siegert Stefanie, Behnke Silvia, Prados-Rosales Rafael, Casadevall Arturo, Lüscher Thomas F, Luther Sanjiv A, Kopf Manfred, Eriksson Urs, Blyszczuk Przemyslaw (2013), Innate signaling promotes formation of regulatory nitric oxide-producing dendritic cells limiting T-cell expansion in experimental autoimmune myocarditis., in Circulation
, 127(23), 2285-94.
Weber M., Hauschild R., Schwarz J., Moussion C., de Vries I., Legler D. F., Luther S. A., Bollenbach T., Sixt M. (2013), Interstitial Dendritic Cell Guidance by Haptotactic Chemokine Gradients, in Science
, 339(6117), 328-332.
Chai Qian, Onder Lucas, Scandella Elke, Gil-Cruz Cristina, Perez-Shibayama Christian, Cupovic Jovana, Danuser Renzo, Sparwasser Tim, Luther Sanjiv A, Thiel Volker, Rülicke Thomas, Stein Jens V, Hehlgans Thomas, Ludewig Burkhard (2013), Maturation of lymph node fibroblastic reticular cells from myofibroblastic precursors is critical for antiviral immunity., in Immunity
, 38(5), 1013-24.
Auderset Floriane, Schuster Steffen, Fasnacht Nicolas, Coutaz Manuel, Charmoy Mélanie, Koch Ute, Favre Stéphanie, Wilson Anne, Trottein François, Alexander James, Luther Sanjiv A, MacDonald H Robson, Radtke Freddy, Tacchini-Cottier Fabienne (2013), Notch signaling regulates follicular helper T cell differentiation., in Journal of immunology (Baltimore, Md. : 1950)
, 191(5), 2344-50.
It is within the T cell rich zone of secondary lymphoid organs (SLO) that dendritic cells (DC) present the captured pathogens to recirculating T cells in order to activate the rare antigen-specific T cells. This zone is characterized by a sponge-like cellular network made of fibroblasts, called T zone fibroblastic reticular cells (FRC or TRC). Rather than being only structural cells, several laboratories including mine have established important roles for FRC in lymph node (LN) homeostasis and immune response. We could show that FRC not only regulate T cell and DC trafficking by producing CCL19 and CCL21 but also T cell homeostasis by secreting IL-7. More recently, we and others demonstrated a regulatory role for FRC as they attenuated antigen-specific T cell proliferation via nitric oxide production. Despite this recent progress we still have a very incomplete understanding of the development, hetereogeneity and function of this ‘novel’ cell type. Over the last nine years my laboratory has developed the technology and expertise to identify, isolate, culture and characterize FRC at the phenotypic and functional level. We propose to use this expertise to characterize aspects of LN FRC development as well as to identify novel functions in homeostasis, adaptive immunity and tolerance. Aim 1: Characterization of FRC heterogeneity in murine lymph nodes going from phenotype to functionAim 2: Defining the immunoregulatory role of FRC in adaptive immunity and toleranceAim 3: Use of Cre-lox technology to study FRC development and function