| Literature DB >> 34343136 |
Anaïs Levescot1, Margaret H Chang1,2, Julia Schnell1,3, Nathan Nelson-Maney1, Jing Yan1,4, Marta Martínez-Bonet1, Ricardo Grieshaber-Bouyer1, Pui Y Lee1,2, Kevin Wei1, Rachel B Blaustein1, Allyn Morris1, Alexandra Wactor1, Yoichiro Iwakura5, James A Lederer6, Deepak A Rao1, Julia F Charles1,4, Peter A Nigrovic1,2.
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.Entities:
Keywords: Autoimmune diseases; Autoimmunity; Inflammation; Rheumatology; T cells
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Year: 2021 PMID： 34343136 PMCID： PMC8439607 DOI： 10.1172/JCI141008
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808