Fig. 1.

Potential role of lymph node stromal cell aging in transplantation. A Structurally intact (1) FRC reticular network, (2) lymphatic vasculature, and HEV (not shown) in the adult LN support the homing and retention of tolerogenic DCs and Tregs [180, 181]. Such a lymph node near the allograft transplant in mice promotes the survival of grafted tissue by a variety of mechanisms that involve the induction of tolerance to the antigens expressed in the grafted tissue ⁵⁴. Further, (3) FRC-mediated diverse immunosuppressive pathways constrain effector T cell activation, proliferation, and differentiation leading to the generation of an environment favorable to support allograft survival ⁴⁴. B However, in old lymph nodes, numerical loss of LECs and structural deterioration of lymphatics and FRC networks [182] in focal areas in the paracortex (T-cell zones) and/or interfollicular areas (T cell/B cell interphase) might negatively affect the mechanisms that support tolerogenic DCs and Tregs. Further, age-related fibrotic changes (excessive extracellular matrix deposition along reticular network) in the old lymph nodes.³² might obscure the DCs’ and Tregs’ access to signals required to maintain their immunosuppressive function. However, whether FRCs retain their capacity to inhibit polyclonal effector T cell responses is not known, but age-related inflammatory changes in the lymph nodes are capable of influencing FRC function and needs systematic investigation. (Created with BioRender.com)