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

Anaïs Levescot, Margaret H Chang, Julia Schnell, Nathan Nelson-Maney, Jing Yan, Marta Martínez-Bonet, Ricardo Grieshaber-Bouyer, Pui Y Lee, Kevin Wei, Rachel B Blaustein, Allyn Morris, Alexandra Wactor, Yoichiro Iwakura, James A Lederer, Deepak A Rao, Julia F Charles, Peter A Nigrovic.

J Clin Invest. 2021 Sep 15;131(18):e141008.

DOI: 10.1172/JCI141008

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.

IL-1β-driven osteoclastogenic Tregs accelerate bone erosion in arthritis – PubMed (nih.gov)

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