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Cited by 275

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Blockade of the interleukin‐21/interleukin‐21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis

Young, Deborah A., Hegen, Martin, Ma, Hak Ling Margery, Whitters, Matthew J., Albert, Leo M., Lowe, Leslie, Senices, Mayra, Wu, Paul W., Sibley, Barbara, Leathurby, Yelena, Brown, Tom P., Nickerson‐Nutter, Cheryl, Keith, James C., Collins, Mary·2007·Arthritis & Rheumatism
DOI 10.1002/art.22452
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Abstract

Objective: Interleukin‐21 (IL‐21) is a T cell–derived cytokine that modulates T cell, B cell, and natural killer cell responses. In this study, the effects of blocking IL‐21 were examined in 2 rodent models of rheumatoid arthritis (RA) to determine whether IL‐21 contributes to their pathologic processes. Methods: DBA/1 mice were immunized with bovine type II collagen and then treated with murine IL‐21 receptor Fc fusion protein (IL‐21R.Fc), which was initiated after the onset of arthritis symptoms in 10% of the cohort. The mice were assessed 3 times per week for signs of disease, including histologic features as well as serum cytokine, Ig, and cytokine messenger RNA (mRNA) levels in the paws. In a separate experiment, Lewis rats were immunized with Freund's complete adjuvant followed by administration of IL‐21R.Fc at the peak of inflammation in the joints. Rats were assessed daily for histologic features and for scoring of arthritis severity. In addition, the effects of IL‐21R.Fc on the production of interferon‐γ (IFNγ) by T cells were examined. Results: Treatment of DBA/1 mice with IL‐21R.Fc reduced the clinical and histologic signs of collagen‐induced arthritis. Nonspecific IgG1 levels were decreased in response to treatment. The levels of IL‐6 mRNA in the paws and the serum IL‐6 levels were decreased after treatment with IL‐21R.Fc. IFNγ mRNA levels were increased in the paws, and the addition of IL‐21R.Fc to collagen‐activated lymph node cultures enhanced the levels of IFNγ. Collagen‐specific spleen cell responses in IL‐21R.Fc–treated mice were observed as reduced levels of IFNγ and increased levels of IL‐6. Treatment of Lewis rats with IL‐21R.Fc after induction of adjuvant‐induced arthritis resulted in reversal of disease signs and improvements in histologic parameters. Conclusion: These findings demonstrate a pathogenic role for IL‐21 in animal models of RA, and support consideration of IL‐21 as a therapeutic target in human RA.

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Metadata

Authors
Young, D. A., Hegen, M., Ma, H. L. M., Whitters, M. J., Albert, L. M., Lowe, L., Senices, M., Wu, P. W., Sibley, B., Leathurby, Y., Brown, T. P., Nickerson‐Nutter, C., Keith, J. C., & Collins, M.
Venue
Arthritis & Rheumatism
Publisher
Wiley
Published
2007-03-28
Volume
56
Issue
4
Pages
1152-1163
ISSN
  • 0004-3591 (ISSN-L)
  • 1529-0131
DOI
10.1002/art.22452
OpenAlex
W1989198317
Cited by
275
References
43
FWCI
19.23
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Blockade of the interleukin‐21/interleukin‐21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. https://app.cochat.ai/papers/10.1002/art.22452
The paper
Young, D. A., Hegen, M., Ma, H. L. M., Whitters, M. J., Albert, L. M., Lowe, L., Senices, M., Wu, P. W., Sibley, B., Leathurby, Y., Brown, T. P., Nickerson‐Nutter, C., Keith, J. C., & Collins, M. (2007). Blockade of the interleukin‐21/interleukin‐21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis & Rheumatism. https://doi.org/10.1002/art.22452

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.