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

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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 languageEnglish
Pages (from-to)1603-1611
Number of pages9
JournalJournal of Clinical Investigation
Volume114
Issue number11
DOIs
Publication statusPublished - 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