Haerle, Peter and Pongratz, Georg and Albrecht, Julia and Tarner, Ingo H. and Straub, Rainer H. (2008) An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+cells. ARTHRITIS AND RHEUMATISM, 58 (8). pp. 2347-2355. ISSN 0004-3591,
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Objective. Activation of the sympathetic nervous system (SNS) ameliorates collagen-induced arthritis (CIA) in the late phase of the disease but aggravates it in the presymptomatic phase. The aim of the present study was to determine whether CD4+CD25+ T cells are influenced by the SNS of mice and play a disease-modifying role in the early symptomatic phase of the disease. Methods. We tested the effects of the SNS on arthritis by transferring CD4+CD25+ T cells from sympathectomized mice immunized with type 11 collagen and from immunized, SNS-intact animals (controls). We further characterized transferred cells by studying forkhead box P3 (FoxP3) expression, cell proliferation, and cytokine secretion. Results. Using anti-dopamine-beta-hydroxylase antibodies for systemic sympathectomy, we noticed a time-dependent disease amelioration (strongest when sympathectomy was performed 7 days before immunization, with no effect 30 days after immunization). When CD4+CD25+ T cells from immunized and sympathectomized animals were transferred into mice with CIA (on day 32), disease severity was reduced compared with that in controls. However, the number of CD4+CD25+FoxP3+ cells and the FoxP3 expression level in CD4+CD25+ cells were not changed by sympathectomy. In a mixed assay of donor CD4+CD25- and CD4+CD25+ cells, proliferation was reduced when cells from sympathectomized animals were studied. In the same assay, secretion of tumor necrosis factor, interleukin-17 (IL-17), IL-10, and IL-4 (not interferon-gamma) was markedly reduced when cells were taken from sympathectomized animals. Culture of CD4+CD25+ cells with norepinephrine (10(-5)M) for 24 hours before transfer worsened the arthritis. Conclusion. The SNS increases disease severity in the early phase of symptomatic CIA by stimulating several proinflammatory aspects of CD4+CD25+ T cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; ADJUVANT-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; TISSUE; INFLAMMATION; AFFERENTS; EFFERENTS; RECEPTOR; INJURY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 09:59 |
| Last Modified: | 26 Oct 2020 09:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30494 |
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