Figure 3.

Role of T lymphocytes during osteoimmunology. Under physiological conditions, the balance between the osteolytic activity of T-helper type-17 (Th17) lymphocytes and bone protective activity of T regulatory (Treg) lymphocytes controls the maintenance of bone tissue homeostasis. Th17 lymphocytes express the transcription factor retinoid acid receptor-related orphan nuclear receptor C2 (RORC2) and induce osteoclastogenesis and activation of mature osteoclasts by producing tumor necrosis factor (TNF)-α, interleukin (IL)-17A, and receptor-activator of nuclear factor κB ligand (RANKL). Treg lymphocytes express the transcription factor forkhead box P3 (Foxp3), overexpress the cell surface marker CD25, and inhibit osteoclastogenesis and osteoclast activity mainly by producing transforming growth factor (TGF)-β1 and IL-10. It is noteworthy that Foxp3⁺CD25^high Treg lymphocytes can directly inhibit the differentiation, proliferation, and function of RORC2⁺ Th17 lymphocytes. Moreover, Foxp3⁺CD25^high Treg lymphocytes can promote the production of Wnt10b by CD8⁺ T lymphocytes, which induces the differentiation of osteoblasts precursors through the Wnt-β-catenin-signaling pathway and consequently promotes bone formation (Created with BioRender.com).