U1 RNA induces innate immunity signaling

Robert W. Huffman, Tal Gazitt, Mark F. Foecking, Robert A. Ortmann, Michael Misfeldt, Rebecca Jorgenson, Steven L. Young, Eric L Greidinger

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Objective. The U1-70-kd RNP is a prominent target of autoimmunity in connective tissue diseases. In this study, we explored whether its endogenous ligand, U1 RNA, mediates a proimmune signal and may be immunogenic. Methods. We assayed the proliferation of control and MyD88-knockout splenocytes in response to in vitro-synthesized U1 RNA, and measured interleukin-6 (IL-6) and IL-8 secretion induced by U1 RNA in a human cell line competent for signaling through Toll-like receptor 3 (TLR-3) and TLR-5. Results. Treatment with U1 RNA or with poly(I-C), a known agonist of TLR-3, induced approximately twice as much control splenocyte proliferation as did treatment with RNase-digested U1 RNA. Proliferation in response to either poly(I-C) or U1 RNA by MyD88-knockout splenocytes was similarly attenuated. Similar to polyd-C), U1 RNA induced significant secretion of both IL-6 and IL-8 from a TLR-3-expressing human cell line; in contrast, the TLR-5 agonist flagellin induced predominantly IL-8 secretion. Pretreatment of U1 RNA with RNase abolished IL-6 and IL-8 secretion. Conclusion. U1 RNA is capable of inducing manifestations consistent with TLR-3 activation. The ability of U1 RNA (which has a substantial double-stranded secondary structure) to activate TLR-3 may contribute to the immunogenicity of the U1-70-kd autoantigen. Stimulation of innate immunity by native MNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins.

Original languageEnglish
Pages (from-to)2891-2896
Number of pages6
JournalArthritis and Rheumatism
Volume50
Issue number9
DOIs
StatePublished - Sep 1 2004

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Innate Immunity
Toll-Like Receptor 3
Interleukin-8
Interleukin-6
Ribonucleases
Autoimmunity
U1 small nuclear RNA
Flagellin
Cell Line
Connective Tissue Diseases
RNA-Binding Proteins
Autoantigens
Ligands

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Huffman, R. W., Gazitt, T., Foecking, M. F., Ortmann, R. A., Misfeldt, M., Jorgenson, R., ... Greidinger, E. L. (2004). U1 RNA induces innate immunity signaling. Arthritis and Rheumatism, 50(9), 2891-2896. https://doi.org/10.1002/art.20428

U1 RNA induces innate immunity signaling. / Huffman, Robert W.; Gazitt, Tal; Foecking, Mark F.; Ortmann, Robert A.; Misfeldt, Michael; Jorgenson, Rebecca; Young, Steven L.; Greidinger, Eric L.

In: Arthritis and Rheumatism, Vol. 50, No. 9, 01.09.2004, p. 2891-2896.

Research output: Contribution to journalArticle

Huffman, RW, Gazitt, T, Foecking, MF, Ortmann, RA, Misfeldt, M, Jorgenson, R, Young, SL & Greidinger, EL 2004, 'U1 RNA induces innate immunity signaling', Arthritis and Rheumatism, vol. 50, no. 9, pp. 2891-2896. https://doi.org/10.1002/art.20428
Huffman RW, Gazitt T, Foecking MF, Ortmann RA, Misfeldt M, Jorgenson R et al. U1 RNA induces innate immunity signaling. Arthritis and Rheumatism. 2004 Sep 1;50(9):2891-2896. https://doi.org/10.1002/art.20428
Huffman, Robert W. ; Gazitt, Tal ; Foecking, Mark F. ; Ortmann, Robert A. ; Misfeldt, Michael ; Jorgenson, Rebecca ; Young, Steven L. ; Greidinger, Eric L. / U1 RNA induces innate immunity signaling. In: Arthritis and Rheumatism. 2004 ; Vol. 50, No. 9. pp. 2891-2896.
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