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

Levescot A, Chang MH, Schnell J, Nelson-Maney N, Yan J, Martínez-Bonet M, Grieshaber-Bouyer R, Lee PY, Wei K, Blaustein RB, Morris A, Wactor A, Iwakura Y, Lederer JA, Rao DA, Charles JF, Nigrovic PA (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Journal of Clinical Investigation American Society for Clinical Investigation

Book Volume: 131

Article Number: e141008

Journal Issue: 18

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.

Authors with CRIS profile

Ricardo Grieshaber Bouyer

Involved external institutions

Brigham and Women's Hospital (BWH) US United States (USA) (US) Tokyo University of Science / 東京理科大学 (Tōkyō Rika Daigaku) JP Japan (JP)

How to cite

APA:

Levescot, A., Chang, M.H., Schnell, J., Nelson-Maney, N., Yan, J., Martínez-Bonet, M.,... Nigrovic, P.A. (2021). IL-1β–driven osteoclastogenic Tregs accelerate bone erosion in arthritis. Journal of Clinical Investigation, 131(18). https://doi.org/10.1172/JCI141008

MLA:

Levescot, Anaïs, et al. "IL-1β–driven osteoclastogenic Tregs accelerate bone erosion in arthritis." Journal of Clinical Investigation 131.18 (2021).

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