The transcription factor SpiB regulates the fibroblastic reticular cell network and CD8 + T-cell responses in lymph nodes

Fibroblastic reticular cells (FRCs) construct microanatomical niches that support lymph node (LN) homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here, we investigated the role of the transcription factor SpiB tha...

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Bibliographic Details
Published in:Immunology and cell biology 2024-04, Vol.102 (4), p.269-279
Main Authors: Horsnell, Harry L, Cao, Wang Hj, Belz, Gabrielle T, Mueller, Scott N, Alexandre, Yannick O
Format: Article
Language:English
Subjects:
CD8 antigen
Homeostasis
Immune response
Lymph nodes
Transcription factors
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Summary:Fibroblastic reticular cells (FRCs) construct microanatomical niches that support lymph node (LN) homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here, we investigated the role of the transcription factor SpiB that is expressed in LN FRCs. Conditional ablation of SpiB in FRCs impaired the FRC network in the T-cell zone of LNs, leading to reduced numbers of FRCs and altered homeostatic functions including reduced CCL21 and interleukin-7 expression. The size and cellularity of LNs 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 an important regulator of FRC functions and immunity in LNs.
ISSN:0818-9641
1440-1711
DOI:10.1111/imcb.12740