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The Journal of Immunology, 2008, 181, 4433
Copyright © 2008 by The American Association of Immunologists, Inc.
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Comment on "Local Accumulation of FOXP3+ Regulatory T Cells: Evidence for an Immune Evasion Mechanism in Patients with Large Condylomata Acuminata"

Mark R. Goldstein*, Luca Mascitelli{dagger} and Francesca Pezzetta{ddagger}

* Medical Director, Fountain Medical Court, Bonita Springs, FL 34135 {dagger} Medical Service, Comando Brigata Alpina "Julia", Urdine, Italy {ddagger} Cardiology Service Ospedale di Tolmezzo Tolmezzo, Italy

We read the interesting paper by Dr. Cao and colleagues on the role of local regulatory T cells (Tregs) in immune evasion in patients with large condylomata acuminata (1). We suggest that the cholesterol-lowering statin drugs may play a putative role in human papillomavirus (HPV) infection and subsequent genital condylomata propagation.

Statins have been shown to significantly increase the peripheral numbers and functionality of Tregs in vivo by inducing the transcription factor, forkhead box P3 (2). This may further enhance the local immunosuppressive effect of Tregs within the condylomata. Additionally, statins alter cholesterol synthesis in keratinocytes (3) and, as a result, may impair cutaneous permeability barrier function, facilitating HPV infection.

Moreover, the immunosuppressive effect of statins, by increasing Treg numbers and function, may allow the persistence of HPV type 16 and the progression of viral-induced intraepithelial neoplasia (4). Physicians need to be vigilant for the worsening of HPV in patients on statin therapy. This is of particular importance, since the American Academy of Pediatrics has recently proposed using statins in some children as early as 8 years of age (5).

References

  1. Cao, Y., J. Zhao, Z. Lei, S. Shen, C. Liu, D. Li, J. Liu, G.-X. Shen, G.-M. Zhang, Z.-H. Feng, B. Huang. 2008. Local accumulation of FOXP3+ regulatory T cells: evidence for an immune evasion mechanism in patients with large condylomata acuminata. J. Immunol. 180: 7681-7686. [Abstract/Free Full Text]
  2. Mausner-Fainberg, K., G. Luboshits, A. Mor, S. Maysel-Auslender, A. Rubinstein, G. Keren, J. George. 2008. The effect of HMG-CoA reductase inhibitors on naturally occurring CD4+CD25+ T cells. Atherosclerosis 197: 829-839. [Medline]
  3. Feingold, K. R.. 2007. The role of epidermal lipids in cutaneous permeability barrier homeostasis. J. Lipid Res. 48: 2531-2546. [Abstract/Free Full Text]
  4. Molling, J. W., T. J. de Gruijl, J. Glim, M. Moreno, L. Rozendaal, C. J. Meijer, A. J. van den Ertwegh, R. J. Scheper, M. E. von Blomberg, H. J. Bontkes. 2007. CD4+CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia. Int. J. Cancer 121: 1749-1755. [Medline]
  5. Daniels, S. R., F. Greer, the Committee on Nutrition 2008. Lipid screening and cardiovascular health in childhood. Pediatrics 122: 198-208. [Abstract/Free Full Text]




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