A major lipid raft protein raftlin modulates T cell receptor signaling and enhances Th17-mediated autoimmune responses

Kazuko Saeki, Satoru Fukuyama, Toranoshin Ayada, Mako Nakaya, Daisuke Aki, Giichi Takaesu, Toshikatsu Hanada, Yumiko Matsumura, Takashi Kobayashi, Ryusuke Nakagawa, Akihiko Yoshimura

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34 Citations (Scopus)

Abstract

The membrane microdomains known as lipid rafts have been shown to act as platforms for the initiation of various receptor signals. Through proteomic analysis, we have identified a novel protein termed Raftlin (raft-linking protein) as a major protein in lipid rafts. To determine the physiological and immunological functions of Raftlin in mammals, we generated Raftlin-deficient mice, as well as Raftlin-transgenic (Tg) mice. Although Raftlin was originally identified in B cells, we observe no severe abnormalities in the B cells of these mice, presumably due to a high expression of Raftlin-homologue (Raftlin-2). T cells, in contrast, expressed a substantial amount of Raftlin but no Raftlin-2. In Raftlin-deficient mice, T cell-dependent Ab production was reduced, and experimental autoimmune encephalomyelitis, a Th17-dependent autoimmune disease model, was ameliorated. In Raftlin-Tg mice, in contrast, Ab production was enhanced and experimental autoimmune encephalomyelitis was more severe. Cytokine production, especially that of IL-17, was reduced in Raftlin-deficient T cells, while it was enhanced in Raftlin-Tg T cells. We found that these changes were associated with the strength of the TCR-mediated signals. Importantly, localization of Lck protein in the lipid rafts was enhanced by Raftlin overexpression and reduced by Raftlin deficiency. These data indicate that Raftlin modulates TCR signals and is necessary for the fine-tuning of T cell-mediated immune responses.

Original languageEnglish
Pages (from-to)5929-5937
Number of pages9
JournalJournal of Immunology
Volume182
Issue number10
DOIs
Publication statusPublished - 2009 May 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Saeki, K., Fukuyama, S., Ayada, T., Nakaya, M., Aki, D., Takaesu, G., Hanada, T., Matsumura, Y., Kobayashi, T., Nakagawa, R., & Yoshimura, A. (2009). A major lipid raft protein raftlin modulates T cell receptor signaling and enhances Th17-mediated autoimmune responses. Journal of Immunology, 182(10), 5929-5937. https://doi.org/10.4049/jimmunol.0802672