Experimental Dermatology 2011-05-01

Resting but not CpG stimulated keratinocytes suppress autologous T-helper cell proliferation--importance of PGE2 and T regulatory function.

Verena Kopfnagel, Thomas Werfel, Miriam Wittmann

Index: Exp. Dermatol. 20(5) , 394-400, (2011)

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Abstract

In the last decade, keratinocytes have increasingly been recognized to actively participate in the skin immune response. However, their influence on infiltrating lymphocytes - abundantly found in e.g. atopic and psoriatic inflammation - is still controversial. In this study, we aimed to investigate the influence of keratinocytes on T-cell proliferation by use of an autologous co-culture model. Because the skin has an important function with regard to detecting invading pathogens, we also investigated the influence of pathogen-associated molecular pattern on keratinocyte - T-cell interaction. We observed a clear inhibition of T-cell proliferation by co-cultured keratinocytes. This effect was found to be mediated by PGE2, as T-cell proliferation was recovered in the presence of the PGE2 inhibitor indometacin. Furthermore, presence of keratinocytes led to enhanced expression of the T regulatory cell-specific transcription factor Foxp3 in the CD4+CD25+ T-cell population which also showed regulatory function. Interestingly, the presence of the TLR9 ligand CpG was able to prevent the inhibition of T-cell proliferation. This was paralleled by a reduced PGE2 production by keratinocytes and a down-regulated T regulatory cell function. Our results indicate that the inhibitory capacity of keratinocytes in the skin is strongly influenced by the surrounding micromillieu.© 2011 John Wiley & Sons A/S.