Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population

Wang et al. 10.1073/pnas.0709592105.

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Fig. 6. The effects of MK deficiency on microglia/macrophage activity and the CD4+/CD8+ T cell population. (a) mRNA expression of antigen-presentation-related molecules, inflammatory cytokines, and chemokines in microglia and macrophages from WT and Mdk-/- mice was examined with or without LPS and IFN-g stimulation. (b) Flow-cytometric analysis of CD4+ T cells and CD8+ T cells from the spleens, mesenteric lymph nodes (MLN), and popliteal lymph nodes (PLN) at the onset of EAE (12-14 days after immunization) in WT and Mdk-/- mice. (c and d) The percentages of CD4+ T cells (c) and CD8+ T cells (d) among all of the mononuclear cells. Data represent the means ± SD (n = 3).





Fig. 7. In vivo depletion of the Treg cells by treatment with anti-CD25 monoclonal antibodies. Mdk-/- mice were i.p. injected with anti-CD25 monoclonal antibodies (PC61); 4 days later, peripheral blood mononuclear cells (PBMCs) or splenocytes were collected and labeled with anti-CD4 and anti-CD25 monoclonal antibodies (7D4), which bind to CD25 noncompetitively with PC61. Flow-cytometric analysis demonstrated that the Treg cell population was effectively depleted from peripheral blood and lymphoid tissue after PC61 administration.





Fig. 8. Proposal mechanism of suppression of Treg cell expansion by MK. CD4+CD25+ T cell differentiate into Treg via sequential activation of JAK1/3, STAT5, and Foxp3. Foxp3 is negatively regulated by tyrosine phosphatase SHP-2, which is a critical suppressor of STAT5. MK reduces Foxp3 expression by up-regulating SHP-2.

This Article

  1. Published online before print March 4, 2008, doi: 10.1073/pnas.0709592105 PNAS March 11, 2008 vol. 105 no. 10 3915-3920
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