Unknown

Dataset Information

0

IL-1β-driven osteoclastogenic Tregs accelerate bone erosion in arthritis.


ABSTRACT: IL-1β is a proinflammatory mediator with roles in innate and adaptive immunity. Here we show that IL-1β contributes to autoimmune arthritis by inducing osteoclastogenic capacity in Tregs. Using mice with joint inflammation arising through deficiency of the IL-1 receptor antagonist (Il1rn-/-), we observed that IL-1β blockade attenuated disease more effectively in early arthritis than in established arthritis, especially with respect to bone erosion. Protection was accompanied by a reduction in synovial CD4+Foxp3+ Tregs that displayed preserved suppressive capacity and aerobic metabolism but aberrant expression of RANKL and a striking capacity to drive RANKL-dependent osteoclast differentiation. Both Il1rn-/- Tregs and wild-type Tregs differentiated with IL-1β accelerated bone erosion upon adoptive transfer. Human Tregs exhibited analogous differentiation, and corresponding RANKLhiFoxp3+ T cells could be identified in rheumatoid arthritis synovial tissue. Together, these findings identify IL-1β-induced osteoclastogenic Tregs as a contributor to bone erosion in arthritis.

SUBMITTER: Levescot A 

PROVIDER: S-EPMC8439607 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

2021-09-06 | GSE183254 | GEO
| PRJNA759793 | ENA
| S-EPMC8121448 | biostudies-literature
2019-11-23 | GSE132832 | GEO
| S-EPMC9770512 | biostudies-literature
| S-EPMC5995354 | biostudies-literature
| S-EPMC5125876 | biostudies-literature
| S-EPMC6971916 | biostudies-literature
| S-EPMC8756407 | biostudies-literature
| S-EPMC7710301 | biostudies-literature