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10.1002/art.38735

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suck abstract from ncbi


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pmid24909430
      Arthritis+Rheumatol 2014 ; 66 (9 ): 2601-12
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  • Interleukin-21 promotes germinal center reaction by skewing the follicular regulatory T cell to follicular helper T cell balance in autoimmune BXD2 mice #MMPMID24909430
  • Ding Y ; Li J ; Yang P ; Luo B ; Wu Q ; Zajac AJ ; Wildner O ; Hsu HC ; Mountz JD
  • Arthritis Rheumatol 2014[Sep]; 66 (9 ): 2601-12 PMID24909430 show ga
  • OBJECTIVE: Follicular regulatory T (Tfr) cells act as the regulatory counterpart of follicular helper T (Tfh) cells to suppress germinal center (GC) B cell differentiation. We recently showed that interleukin-21 (IL-21) promoted Tfh cell differentiation in autoimmune BXD2 mice that develop spontaneous GCs. This study was undertaken to determine the modulatory effects of IL-21 on Tfr cells and the Tfr cell to Tfh cell balance in BXD2 mice. METHODS: The percentage and phenotype of Tfr cells were determined in BXD2 and BXD2-IL21(-/-) mice. The effects of IL-21 on Tfr cells and the Tfr cell:Tfh cell ratio were evaluated. Sorted Tfr cells from BXD2-IL21(-/-) mice were cocultured with Tfh cells and B cells, or transferred into BXD2 mice to determine their function. RESULTS: The percentages and numbers of GC B cells and Tfh cells were significantly reduced, but the percentage of Tfr cells was 2-fold higher in BXD2-IL21(-/-) mice than in wild-type BXD2 mice. Administration of AdIL-21 to BXD2-IL21(-/-) mice decreased the percentages and numbers of Tfr cells and the Tfr cell:Tfh cell ratio but increased the number of GC B cells in the spleen. Recombinant murine IL-21 suppressed FoxP3 and significantly reduced Tgfb1, Il2, and Gitr but enhanced Il21, Il6, Pd1, Cxcr5, and Icos expression in Tfr cells. IL-21 also counteracted Tfr cell-mediated inhibition of antibody secretion in the Tfh cell-B cell coculture system. Transfer of Tfr cells into young BXD2 mice reduced GC size and decreased the numbers of autoantibody-producing B cells. CONCLUSION: Our findings indicate that high levels of IL-21 selectively enhance Tfh cell differentiation but inhibit Tfr cell commitment and the suppressive function of Tfr cells on Tfh cells and B cells, suggesting that IL-21 skews the balance from Tfr cells to Tfh cells to promote autoreactive GC reactions in BXD2 mice.
  • |Animals [MESH]
  • |Autoantibodies/immunology [MESH]
  • |Cell Differentiation/*immunology [MESH]
  • |Germinal Center/cytology/immunology/*metabolism [MESH]
  • |Interleukin-21 [MESH]
  • |Interleukins/genetics/*metabolism [MESH]
  • |Mice [MESH]
  • |T-Lymphocytes, Helper-Inducer/cytology/immunology/*metabolism [MESH]


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