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Regulatory T cells and toll-like receptors: regulating the regulators
  1. Roger Sutmuller1,2,
  2. Anja Garritsen2,
  3. Gosse J Adema1
  1. 1
    Tumor Immunology Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  2. 2
    Target Discovery Oss, NV Organon, Oss, The Netherlands
  1. Roger P M Sutmuller, Target Discovery Oss, NV Organon, 5340 BH Oss, The Netherlands; Roger.Sutmuller{at}


Regulatory T cells (Treg) play a crucial role in maintaining control of leucocytes. Several studies have shown that in vivo Treg depletion results in autoimmune syndromes like thyroiditis, gastritis, diabetes mellitus and colitis, but at the same time, may also result in improved anti-tumour vaccination. Although Treg are recognised to maintain peripheral tolerance in healthy individuals, recent research has shown that Treg also suppress immune responses during infections to prevent tissue damage. How the Treg themselves are regulated is still under investigation. Their suppressive activity must be regulated in order to allow for the effective elimination of pathogens. Until recently, this control of Treg function was found to be through modulation via cytokines or by stimulation via co-stimulatory molecules on antigen-presenting cells. It is now demonstrated, however, that the presence of pathogens can be communicated to Treg directly through toll-like receptors (TLRs). Up until now, Treg have been reported to respond to ligands for TLR2, 4, 5 and 8, and different TLRs can have alternative effects on Treg resulting in more suppression or, in contrast, abrogation of suppression. As TLRs can also recognise endogenous proteins, such as heat shock proteins, it is tempting to speculate on the role of these proteins in modulating Treg function during chronic inflammation. In this review, we will discuss the implications of TLR engagement on Treg and any consequences this may have for chronic autoinflammatory diseases like rheumatoid arthritis (RA).

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  • Funding: RS was supported at the UMC St Radboud by The Netherlands Scientific Organization (NWO: Veni 916.56.130).

  • Competing interests: None.

  • Abbreviations:
    antigen-presenting cells
    pathogen-associated molecular patterns
    rheumatoid arthritis
    T cell receptor
    toll-like receptors
    regulatory T cells

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