Rheumatology Advance Access originally published online on March 1, 2005
Rheumatology 2005 44(6):819-820; doi:10.1093/rheumatology/keh582
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LETTER TO THE EDITOR |
A role for TARC/CCL17, a CC chemokine, in New Zealand mice
Institute of Rheumatology, Tokyo Women's Medical University, Tokyo and 1 Toin Human Science and Technology Center, Department of Material Science and Technology, Toin University of Yokohama, Yokohama, Japan
Correspondence to: H. Okamoto, Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku, Tokyo 162-0054, Japan. E-mail: hokamoto{at}ior.twmu.ac.jp
SIR, Systemic lupus erythematosus (SLE) is an autoimmune disease in which peripheral helper T2 (Th2) cells have traditionally been considered to predominate. However, contradicting results regarding helper T1 (Th1) predominance in SLE have recently been reported, so the issue of Th1 vs Th2 predominance in SLE patients remains unresolved. To clarify this matter, we have recently published data demonstrating that the plasma levels of thymus- and activation-regulated chemokine (TARC)/CCL17 were highest in untreated SLE patients, and were higher in immunosuppressive-treated SLE patients than in rheumatoid arthritis (RA) patients and healthy donors [1]. TARC/CCL17, a Th2-type CC chemokine, is one of the high-affinity ligands for CCR4, a chemokine receptor that is predominantly expressed on Th2 cells [2]. TARC/CCL17 is reported to be high in plasma from patients with allergic diseases, such as bronchial asthma and atopic dermatitis [3, 4]. These data indicate that Th2 is predominant in the primary pathogenesis of SLE.
(NZB x NZW)F1 (B/WF1) mice spontaneously develop systemic autoimmune disorders resembling SLE in humans [5, 6]. It is characterized by production of a variety of IgG autoantibodies and massive deposition of immune complexes in glomeruli in the kidney. The mice develop elevated levels of IgM anti-double-stranded DNA (anti-dsDNA) antibodies [7]. Between 3 and 4 months of age, B cells undergo class-switching from IgM to IgG of anti-dsDNA antibodies. Thereafter, the mice develop lupus nephritis and more than 95% of these mice die from renal failure before reaching 12 months. SLE disease is B cell- and CD4+ Th cell-dependent [8] and can be treated by immune intervention, such as immunosuppressive drugs, T-cell costimulatory blockade and anti-CD4 monoclonal antibody-mediated therapy. It is now widely accepted that dysregulation of Th1/Th2 balance is a general feature in the onset, progression and prognosis of autoimmune diseases [9, 10].
Here, we show the role of the Th2 chemokine TARC/CCL17 in NZB/W F1 mice by comparing the plasma concentrations of TARC/CCL17 among NZB/W F1 mice, parental strains [New Zealand Black (NZB) and New Zealand White (NZW)] and control mice (C57BL/6).
Plasma samples were obtained from 36 mice (NZB, n = 3, age 2 months; NZB, n = 3, age 6 months; NZB, n = 3, age 9 months; NZW, n = 3, age 2 months; NZW, n = 3, age 6 months; NZW, n = 3, age 9 months; NZB/WF1, n = 3, age 2 months; NZB/WF1, n = 3, age 6 months; NZB/WF1, n = 3, age 9 months; C57BL/6, n = 3, age 2 months; C57BL/6, n = 3, age 6 months; and C57BL/6, n = 3, age 9 months). Blood samples were centrifuged and the plasma was frozen at –80°C until tested. TARC/CCL17 concentrations were determined by enzyme-linked immunosorbent assay using the Quantikine mouse TARC Immunoassay (R&D Systems, Minneapolis, MN, USA). Statistical analyses were performed with the Mann–Whitney test. Ethical approval for this study was given by the guidelines for animal experimentation of the Tokyo Women's Medical University. Plasma levels of TARC/CCL17 were significantly higher in NZB/W F1 mice at 6 months than in the other mice (P = 0.049, Mann–Whitney U-test; Fig. 1). There was a tendency for an age-related increase in TARC/CCL17 in plasma from the parental strains, NZB and NZW. However, in normal mice (C57BL/6), we were unable to see this tendency (Fig. 1). NZB/W F1 mice spontaneously develop systemic autoimmune disorders resembling SLE in humans. In addition, between 3 and 4 months of age, B cells undergo a class switch from IgM to IgG of anti-dsDNA antibodies. This process is thought to be dependent on helper T cells. Therefore, our observation might reflect this class-switching process, suggesting that Th2 cells contribute significantly to this class switch, which plays important roles in the pathogenesis of autoimmunity in NZB/W F1 mice. Further studies should be performed to analyse the histological findings of lupus nephritis and circulating TARC/CCL17 levels in lupus-prone mice.
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References
- Okamoto H, Koizumi K, Yamanaka H et al. A role for TARC/CCL17, a CC chemokine, in systemic lupus erythematosus. J Rheumatol 2003;11:2369–73.
- Sallusto F, Lanzavecchia A, Mackay CR. Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. Immunol Today 1998;19:568–74.[CrossRef][Web of Science][Medline]
- Sekiya T, Yamada H, Yamaguchi M et al. Increased levels of a TH2-type CC chemokine thymus and activation-regulated chemokine (TARC) in serum and induced sputum of asthmatics. Allergy 2002;57:173–7.[CrossRef][Web of Science][Medline]
- Kakinuma T, Nakamura K, Wakugawa M et al. Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity. J Allergy Clin Immunol 2001;107:535–41.[CrossRef][Web of Science][Medline]
- Kotzin, B.L. Systemic lupus erythematosus. Cell 1996;85:303–6.[CrossRef][Web of Science][Medline]
- Shirai T, Hirose S, Okada T, Nishimura H. Immunology and immunopathology of the autoimmune disease of NZB and related mouse strains. In: Rihova EB, Vetvicka V, eds. Immunological disorders in mice. Boca Raton, FL: CRC Press, 1991:95–136.
- Stott DI, Merino J, Schurmans S et al. Expression of anti-DNA clonotypes and the role of helper T-lymphocytes during the autoimmune response in mice tolerant to alloantigens. Autoimmunity 1988;1:253–66.[CrossRef][Medline]
- Humbert M, Galanaud P. B-lymphocyte hyperreactivity and differentiation factors of T-lymphocytes in systemic lupus erythematosus. Ann Med Interne (Paris) 1990;141:213–6.[Medline]
- Wofsy D, Chiang NY, Greenspan JS, Ermak TH. Treatment of murine lupus with monoclonal antibody to L3T4. I. Effects on the distribution and function of lymphocyte subsets and on the histopathology of autoimmune disease. J Autoimmun 1988;1:415–31.[CrossRef][Web of Science][Medline]
- Wofsy D. Treatment of murine lupus with anti-CD4 monoclonal antibodies. Immunol Ser 1993;59:221–36.[Medline]
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