Nucleic acid-stimulated antigen-presenting cells trigger T cells to induce disease in a rat transfer model of inflammatory arthritis.

Abstract

Autoimmune responses to heterogeneous nuclear ribonucleproteins (hnRNP) occur in many systemic autoimmune diseases, particularly in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. In RA, humoral and/or cellular autoimmunity to hnRNP-A2/B1 is the most prominent anti-nuclear reactivity, being detectable in more than 50% of patients. However, its pathogenic role has not been fully elucidated yet. Here, we report that splenocytes from rats with pristane-induced arthritis transfer disease after in vitro restimulation with hnRNP-A/B antigens. Remarkably, disease transfer can be blocked by nuclease treatment of hnRNPs and is also achieved with splenocytes stimulated with hnRNP-A/B associated DNA or RNA oligonucleotides (ON) alone. Induction of proinflammatory cytokines in splenocytes stimulated with hnRNP-A/Bs or ONs involves Toll-like receptors (TLR) 7 and 9 but not TLR3. Furthermore, although T cells are the main mediators of disease transfer they require restimulation with TLR-activated antigen-presenting cells such as macrophages in order to become arthritogenic. Thus, the autoantigenic properties of hnRNPs appear to be mediated by their associated nucleic acids binding to TLR7 and 9. Our data explain the specific selection of hnRNP-A2/B1 as autoantigen in RA and reveal the requirement of interaction between innate and adaptive immunity to initiate and drive inflammation in autoimmune arthritis.

• Authors: Markus H Hoffmann, Karl Skriner, Sonja Herman, Christoph Baumann, Carl-Walter Steiner, Caroline Ospelt, Brigitte Meyer, Andreas Gleiss, Jürgen Pfatschbacher, Birgit Niederreiter, Jonatan Tuncel, Gerald Zanoni, Guenter Steiner
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 36 Issue 3-4 Pg. 288-300 (May 2011) ISSN: 1095-9157 [Electronic] England
• PMID: 21439786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Heterogeneous-Nuclear Ribonucleoprotein Group A-B
• TLR7 protein, rat
• Terpenes
• Tlr9 protein, rat
• Toll-Like Receptor 7
• Toll-Like Receptor 9
• pristane

Topics

• Animals
• Antigen-Presenting Cells (immunology)
• Arthritis, Rheumatoid (etiology)
• Heterogeneous-Nuclear Ribonucleoprotein Group A-B (immunology)
• Humans
• Rats
• T-Lymphocytes (immunology)
• Terpenes (toxicity)
• Toll-Like Receptor 7 (physiology)
• Toll-Like Receptor 9 (physiology)