Lymph node fibroblastic reticular cells in health and disease

Fibroblastic reticular cells — which are immunologically specialized myofibroblasts of mesenchymal origin — create a network within lymph nodes that is essential for immunological health through interactions with B cells, T cells, dendritic cells and high endothelial venules. Over the past decade, a series of discoveries relating to fibroblastic reticular cells (FRCs) — immunologically specialized myofibroblasts found in lymphoid tissue — has promoted these cells from benign bystanders to major players in the immune response. In this Review, we focus on recent advances regarding the immunobiology of lymph node-derived FRCs, presenting an updated view of crucial checkpoints during their development and their dynamic control of lymph node expansion and contraction during infection. We highlight the robust effects of FRCs on systemic B cell and T cell responses, and we present an emerging view of FRCs as drivers of pathology following acute and chronic viral infections. Lastly, we review emerging therapeutic advances that harness the immunoregulatory properties of FRCs.