TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice

Reiko Horai; Akiko Nakajima; Katsuyoshi Habiro; Motoko Kotani; Susumu Nakae; Taizo Matsuki; Aya Nambu; Shinobu Saijo; Hayato Kotaki; Katsuko Sudo; Akihiko Okahara; Hidetoshi Tanioka; Toshimi Ikuse; Naoto Ishii; Pamela L. Schwartzberg; Ryo Abe; Yoichiro Iwakura

doi:10.1172/JCI20742

TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice

Reiko Horai, Akiko Nakajima, Katsuyoshi Habiro, Motoko Kotani, Susumu Nakae, Taizo Matsuki, Aya Nambu, Shinobu Saijo, Hayato Kotaki, Katsuko Sudo, Akihiko Okahara, Hidetoshi Tanioka, Toshimi Ikuse, Naoto Ishii, Pamela L. Schwartzberg, Ryo Abe, Yoichiro Iwakura

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

IL-1 receptor antagonist-deficient (IL-1Ra^-/-) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell-deficient IL-1Ra^-/- mice did not develop arthritis, and transfer of IL-1Ra^-/- T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-α deficiency. We found that TNF-α induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-α plays an important role in activating T cells through induction of OX40.

Original language	English
Pages (from-to)	1603-1611
Number of pages	9
Journal	Journal of Clinical Investigation
Volume	114
Issue number	11
DOIs	https://doi.org/10.1172/JCI20742
Publication status	Published - 2004 Dec

ASJC Scopus subject areas

Medicine(all)

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Horai, R., Nakajima, A., Habiro, K., Kotani, M., Nakae, S., Matsuki, T., Nambu, A., Saijo, S., Kotaki, H., Sudo, K., Okahara, A., Tanioka, H., Ikuse, T., Ishii, N., Schwartzberg, P. L., Abe, R., & Iwakura, Y. (2004). TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice. Journal of Clinical Investigation, 114(11), 1603-1611. https://doi.org/10.1172/JCI20742

Horai, R, Nakajima, A, Habiro, K, Kotani, M, Nakae, S, Matsuki, T, Nambu, A, Saijo, S, Kotaki, H, Sudo, K, Okahara, A, Tanioka, H, Ikuse, T, Ishii, N, Schwartzberg, PL, Abe, R & Iwakura, Y 2004, 'TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice', Journal of Clinical Investigation, vol. 114, no. 11, pp. 1603-1611. https://doi.org/10.1172/JCI20742

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title = "TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice",

abstract = "IL-1 receptor antagonist-deficient (IL-1Ra-/-) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell-deficient IL-1Ra-/- mice did not develop arthritis, and transfer of IL-1Ra-/- T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-α deficiency. We found that TNF-α induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-α plays an important role in activating T cells through induction of OX40.",

author = "Reiko Horai and Akiko Nakajima and Katsuyoshi Habiro and Motoko Kotani and Susumu Nakae and Taizo Matsuki and Aya Nambu and Shinobu Saijo and Hayato Kotaki and Katsuko Sudo and Akihiko Okahara and Hidetoshi Tanioka and Toshimi Ikuse and Naoto Ishii and Schwartzberg, {Pamela L.} and Ryo Abe and Yoichiro Iwakura",

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AU - Horai, Reiko

AU - Nakajima, Akiko

AU - Habiro, Katsuyoshi

AU - Kotani, Motoko

AU - Nakae, Susumu

AU - Matsuki, Taizo

AU - Nambu, Aya

AU - Saijo, Shinobu

AU - Kotaki, Hayato

AU - Sudo, Katsuko

AU - Okahara, Akihiko

AU - Tanioka, Hidetoshi

AU - Ikuse, Toshimi

AU - Ishii, Naoto

AU - Schwartzberg, Pamela L.

AU - Abe, Ryo

AU - Iwakura, Yoichiro

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N2 - IL-1 receptor antagonist-deficient (IL-1Ra-/-) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell-deficient IL-1Ra-/- mice did not develop arthritis, and transfer of IL-1Ra-/- T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-α deficiency. We found that TNF-α induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-α plays an important role in activating T cells through induction of OX40.

AB - IL-1 receptor antagonist-deficient (IL-1Ra-/-) mice spontaneously develop autoimmune arthritis. We demonstrate here that T cells are required for the induction of arthritis; T cell-deficient IL-1Ra-/- mice did not develop arthritis, and transfer of IL-1Ra-/- T cells induced arthritis in nu/nu mice. Development of arthritis was also markedly suppressed by TNF-α deficiency. We found that TNF-α induced OX40 expression on T cells and blocking the interaction between either CD40 and its ligand or OX40 and its ligand suppressed development of arthritis. These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-α plays an important role in activating T cells through induction of OX40.

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TNF-α is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice

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