Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Vitamin D Suppresses the Pathogenic Behavior of Primary Th17 Cells from Patients with Early RA in Synovial Fibroblast Activation.

van Hamburg3,  Jan Piet, Asmawidjaja3,  Patrick, Mus3,  Anne-Marie, Hazes2,  Mieke, van Leeuwen1,  Hans, Colin2,  Edgar, Lubberts4,  Erik

Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam
Department of Rheumatology, Erasmus MC, University Medical Center Rotterdam
Departments of Rheumatology and Immunology, Erasmus MC, University Medical Center Rotterdam
Erasmus MC, Rotterdam, ZH, The Netherlands

Introduction:

Vitamin D is a secosteroid hormone that is produced on the skin under the influence of sunlight or is obtained from the diet. In the liver, the inactive precursor vitamin D3 is converted to the hormonal precursor 25-hydroxyvitamin D3 (25(OH)D3). In the kidneys and extrarenal tissue, 25(OH)D3 is converted into its most active metabolite 1,25(OH)2D3. It has been shown that 1,25(OH)2D3 has immunomodulatory effects in many experimental autoimmune models. Recently, we showed that vitamin D modulated Th17 polarization and IL-22 expression by memory T cells from patients with early rheumatoid arthritis and stimulates IL-4 production by PBMC from early RA patients.

Objective:

To identify the effect of vitamin D on the pathogenic behavior of primary Th17 cells on synovial fibroblast (RASF) activation both from patients with early RA.

Methods:

From PBMC of patients with early RA, CCR6+CD45RO+CD4+ Th17 cells were FACS sorted and co-cultured with early RA synovial fibroblasts (RASF) in the absence or presence of Vitamin D. Supernatant of these cultures were analyzed for the production of inflammatory cytokines and matrix metalloproteases (MMPs) with ELISA. Transcription of genes involved in the differentiation and function of T cells or genes expressed by activated RASF were analyzed by quantitative RT-PCR analysis. In addition, TNF-alpha and IL-17A blocking experiments were performed in these co-cultures.

Results:

Th17-RASF co-culture experiments revealed an increase of IL-6, IL-8, and MMP-1 and MMP-3. Vitamin D significantly suppressed the production of IL-6 and MMP-3 in these co cultures. Interestingly, the specific enhanced autocrine production of IL-17 due to this Th17-RASF interaction was significantly inhibited by vitamin D. In addition, markedly suppressed expression of RORgammat and significantly enhanced expression of GATA3 was noted in the presence of vitamin D. No effect of vitamin D was observed on T-bet and FoxP3 expression. In addition, lower IL-22 and enhanced IL-10 production was found in the presence of vitamin D. The regulatory effects of vitamin D on IL-17 production in the Th17-RASF co culture was comparable to neutralizing IL-17 and on IL-6 production comparable to neutralizing TNF or IL-17.

Conclusion:

These data show that vitamin D modulates the pathogenic behavior of primary Th17 cells in their activation of synovial fibroblasts. In addition, vitamin D suppresses the pro-inflammatory IL-17 loop between Th17 and RASF cells. These data suggest that the activation of the vitamin D pathway may have therapeutic potential for the treatment or even prevention of persistent arthritis.

To cite this abstract, please use the following information:
van Hamburg, Jan Piet, Asmawidjaja, Patrick, Mus, Anne-Marie, Hazes, Mieke, van Leeuwen, Hans, Colin, Edgar, et al; Vitamin D Suppresses the Pathogenic Behavior of Primary Th17 Cells from Patients with Early RA in Synovial Fibroblast Activation. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1274
DOI: 10.1002/art.29040

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