Senescence of fibroblastic reticular cells in draining lymph nodes: immunoregulation following transplantation

Abstract

The lymph node (LN) is an intriguing site not only for inducing protective effector immunity but also for inducing tolerance against peripherally encountered antigens such as tissue-specific self-antigens that are regionally drained and through draining lymph nodes (DLNs). The dual functions of DLNs in immunity are attributable at least in part to fibroblastic reticular cells (FRCs), which are a major population of the nonhematopoietic compartment in the LN. In this issue of the JCI, Li, Zhao, and colleagues investigated DLNs in the transplantation setting. The authors demonstrated that, following skin transplantation, the donor mast cell-mediated senescence in FRCs was associated with collagen 1 deposition in DLNs. Systemic administration to mice of FRCs that were expanded ex vivo decreased DLN fibrosis and strengthened the effect of anti-CD40L in prolonging heart allograft survival. These data implicate the DLN as a target for immunomodulatory therapy of transplant rejection.

Figure 1. Model for donor mast cell–mediated senescence of FRCs.

Li, Zhao, and colleagues showed that following transplantation, collagen 1 was deposited in DLNs and fibrosis ensued. Donor mast cells induced senescence of FRCs through LIGHT-HVEM interaction (11). Healthy FRCs deleted activated CD8⁺ T cells and supported Foxp3⁺ Tregs to promote tolerance. Systemic administration of FRCs increased Foxp3⁺ Tregs and promoted tolerance (11). TCR, T cell receptor.