4.3 Article

FoxP3 mRNA splice forms in synovial CD4+T cells in rheumatoid arthritis and psoriatic arthritis

Journal

APMIS
Volume 120, Issue 5, Pages 387-396

Publisher

WILEY
DOI: 10.1111/j.1600-0463.2011.02848.x

Keywords

FoxP3; rheumatoid arthritis; psoriatic arthritis; CD4-positive T-lymphocytes; alternative splicing

Funding

  1. Oak Foundation
  2. Capital Region of Denmark
  3. Danish Rheumatism Association
  4. Velux Foundation
  5. Direktor Einar Hansen og hustru fru Vera Hansens Fond
  6. Familien Hede Nielsens Fond
  7. Margit og Karl Johan Rosenbergs Legat for leddegigt
  8. A. P. Moller Foundation for the Advancement of Medical Science
  9. Grosserer A.V. Lykfeldt og hustrus legat

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Our aim was to elucidate the relative amount of the different splice forms of FoxP3 mRNA in CD4+ T cells in peripheral blood (PB) compared to synovial fluid (SF) in RA and PsA patients. FoxP3 mRNA was measured using a quantitative real-time PCR method. CD4+ T cells were isolated from 17 paired samples of PB and SF from RA and PsA patients, and PB from 10 controls. FoxP3fl and FoxP3D2 mRNA was significantly increased (6.7 and 2.1-fold, respectively) in PB CD4+ T cells from RA patients compared to controls. FoxP3fl and D2 mRNA in SF CD4+ T cells was increased compared to controls in sero-negative RA and PsA, but not in sero-positive RA patients, who had a high FoxP3 expression in both PB and SF. The FoxP3 Delta 2 Delta 7 mRNA was barely detectable in patient samples, and not at all in healthy individuals. We provide evidence of an increased expression of FoxP3 splice forms in synovial CD4+ T cells from RA patients. A skewed, high expression profile of FoxP3, but not CTLA-4, in sero-negative RA and PsA, indicates that synovial CD4+ T cells may represent unique subsets of T cells which have been induced locally or selectively recruited to the joint.

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