The interaction of regulatory T-cells and osteoclasts in health and ageing

Regulatory T cells (Tregs) are part of the adaptive immune system, and their main role is to maintain peripheral tolerance. Emerging evidence suggests that Tregs play a key role in regulating healthy bone mass by driving bone repair and regeneration through inhibition of osteoclast formation. Age-related changes in the immune system can lead to dysregulations in the Treg population, which may ultimately cause bone remodelling imbalance. Bone remodelling is a complex process by which old and/or damaged bone is replaced by new bone. An imbalance in bone remodelling leads to several bone related diseases such as osteoarthritis. The data in this thesis showed a decrease in CD4+Foxp3+ Tregs in peripheral blood in the aged population, as well as a decrease in the possible bone homing Tregs (CXCR4+CD4+Foxp3+). CTX-1 levels, an indicator of bone resorption, in serum did not show any correlation with the levels of Tregs in peripheral blood. In vitro studies supported the interaction of Tregs and osteoclasts, by revealing a lower functional activity of osteoclasts when cultured in the presence Tregs. Data suggested that aged Tregs may present a higher suppressive activity. Spatial localisation of Tregs in murine knee joints showed co-localisation of Tregs and osteoclasts in the subchondral bone. Higher levels of Tregs were observed in the subchondral bone in OA mice and aged WT mice suggesting migration of Tregs towards the site of bone remodelling. Higher presence of Tregs was also linked to higher numbers of osteoclasts during advanced osteoarthritis, which is an indicator of high bone remodelling.