The transcription factor SpiB regulates Fibroblastic Reticular Cell network and CD8+ T cell responses in lymph nodes

Abstract

Fibroblastic Reticular Cells (FRCs) construct microanatomical niches that support lymph node homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here we investigate the role of the transcription factor SpiB that is expressed in lymph node FRCs. Conditional ablation of SpiB in FRCs impaired the FRC network in the T cell zone of lymph nodes, leading to reduced numbers of FRCs and altered homeostatic functions including reduced CCL21 and interleukin-7 expression. The size and cellularity of lymph nodes remained intact in the absence of SpiB but the space between the reticular network increased, indicating that although FRCs were reduced in number they stretched to maintain network integrity. Following virus infection, antiviral CD8+ T cell responses were impaired, suggesting a role for SpiB expression in FRCs in orchestrating immune responses. Together, our findings reveal a new role for SpiB as a critical regulator of FRC functions and immunity in lymph nodes.