Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice.

ABSTRACT: The loss of estrogen (E₂ ) initiates a rapid phase of bone loss leading to osteoporosis in one-half of postmenopausal women, but the mechanism is not fully understood. Here, we show for the first time how loss of E₂ activates low-grade inflammation to promote the acute phase of bone catabolic activity in ovariectomized (OVX) mice. E₂ regulates the abundance of dendritic cells (DCs) that express IL-7 and IL-15 by inducing the Fas ligand (FasL) and apoptosis of the DC. In the absence of E₂ , DCs become long-lived, leading to increased IL-7 and IL-15. We find that IL-7 and IL-15 together, but not alone, induced antigen-independent production of IL-17A and TNFα in a subset of memory T cells (T_MEM ). OVX of mice with T-cell-specific ablatio

SUBMITTER: Cline-Smith A 

PROVIDER: S-EPMC8061311 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature