Abstract EN:

The receptor activator of NF-κB (RANK) is known to control bone mass and development of the skin appendages. This, and its function in epithelial cell biology in general, incited us to investigate the role of RANK in skin and hair follicles (HFs). We show that mice deficient in RANK or RANK-ligand (RANKL) are unable to initiate a new growth phase of the hair cycle and display arrested epidermal homeostasis. Transgenic mice overexpressing RANK in the HF and administration of recombinant RANKL activate the hair cycle and epidermal growth. RANK is expressed by HF stem cells and RANKL is actively transcribed by the growing HF supporting a role of RANK-activation of stem cells for hair cycle entry. In addition to its function in bone and skin, RANK is required for development of lymph nodes (LNs), a feature shared with lymphotoxin β receptor (LTβR). However, LTβR is further involved in the maintenance of LN organization, which had not been demonstrated for RANK. We therefore addressed the question of the function of RANK in LNs beyond development. For this, we took advantage of the transgenic mice overexpressing RANK in the HF, as they displayed a massive post-natal growth of skin-draining LNs. They displayed conserved proportions of hematopoietic and stromal cells, but an increase in the number of small B cell follicles. We showed that skin-derived RANKL induces LN stromal cell proliferation and expression of chemokines and adhesion molecules, resulting in the LN growth. This work highlighted an additional function for RANK-signaling in LNs, namely its control of LN plasticity, and underlines the importance of tissue-derived cues for secondary lymphoid organ homeostasis.