Splenic fibroblastic reticular cells regulate dendritic cell maturation and T-DC interactions required for antiviral immunity

ABSTRACT: Stromal cells construct the architecture of the spleen and provide crucial signals that influence the homeostasis and migration of immune cells in the steady state. Fibroblastic Reticular Cells (FRCs) respond to infection via the regulation of many key structural and functional components. Yet, how spleen FRCs contribute to the induction and maintenance of antiviral T cell responses is still poorly defined. We found that ablation of splenic FRCs impacted the generation of virus-specific CD8 T cell during lymphocytic choriomeningitis virus (LCMV) infection in mice. Imaging revealed that during T cell priming in the presence of FRCs, CD8 T cells clustered in the T cell zone with type 1 conventional dendritic cells (cDC1) before moving to the marginal zone to interact with virus-infected cells. In the absence of FRCs, T cells instead clustered with virus-infected cells and cDC1s in the marginal zone, undergoing suboptimal priming due to reduced TCR signalling and unstable DC-T cell interactions. We found that FRCs regulated the early inflammatory wave required for optimal DC activation in vivo. The absence of FRCs thus resulted in diminished DC activation and impaired capacity to prime T cell responses. We further revealed that the presence of an intact FRC network was crucial for the generation of functional effector T cells. Importantly, these early cellular events orchestrated by FRCs also regulated the generation of protective memory T cells upon resolution of infection. Altogether, our study reveals important roles for FRCs for induction of antiviral T cell responses through support for DC maturation, effector CTL generation and the formation of protective memory T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE274926 | GEO | 2024/08/16

REPOSITORIES: GEO