Maturation of Lymph Node Fibroblastic Reticular Cells from Myofibroblastic Precursors Is Critical for Antiviral Immunity

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

The stromal scaffold of the lymph node (LN) paracortex is built by fibroblastic reticular cells (FRCs). Conditional ablation of lymphotoxin-β receptor (LTβR) expression in LN FRCs and their mesenchymal progenitors in developing LNs revealed that LTβR-signaling in these cells was not essential for the formation of LNs. Although T cell zone reticular cells had lost podoplanin expression, they still formed a functional conduit system and showed enhanced expression of myofibroblastic markers. However, essential immune functions of FRCs, including homeostatic chemokine and interleukin-7 expression, were impaired. These changes in T cell zone reticular cell function were associated with increased susceptibility to viral infection. Thus, myofibroblasic FRC precursors are able to generate the basic T cell zone infrastructure, whereas LTβR-dependent maturation of FRCs guarantees full immunocompetence and hence optimal LN function during infection.