Differentiated keratinocytes are responsible for TNF-alpha regulated production of macrophage inflammatory protein 3 alpha/CCL20, a potent chemokine for Langerhans cells
M. Tohyama et al., Differentiated keratinocytes are responsible for TNF-alpha regulated production of macrophage inflammatory protein 3 alpha/CCL20, a potent chemokine for Langerhans cells, J DERMA SCI, 27(2), 2001, pp. 130-139
The recruitment of immature dendritic cells into the epidermis is a key ste
p in the development of cutaneous immunity, although the mechanism remains
to be clarified. Recently, it was reported that both macrophage inflammator
y protein 3 alpha (MIP-3 alpha)/CCL20 produced by keratinocytes and TNF-a a
re important in recruiting Langerhans cells (LC) to the epidermis. In this
study, we examined the production of MIP-3a by human keratinocytes stimulat
ed with TNF-alpha. Cultured keratinocytes showed enhanced expression of MIP
-3 alpha mRNA and protein when stimulated with TNF-a. In addition, conditio
ned medium from TNF-a-stimulated keratinocyte cultures induced the migratio
n of L1.2 cells expressing CCR6. We next examined the production of MIP-3a
in stratified keratinocytes and found that, in contrast to non-stratified k
eratinocytes, stimulation with TNF-a increased the expression of MIP-3a mRN
A and protein. Moreover, skin samples grown in organ culture and treated wi
th TNF-a showed MIP-3a in the keratinocytes of the spinous layer, but not i
n the basal layer, by immunofluorescence staining. Based on these results,
we postulate that MIP-3a produced by keratinocytes in the spinous layer in
response to TNF-a stimulation is a key chemokine responsible for the epider
mal recruitment of Langerhans cells. (C) 2001 Elsevier Science Ireland Ltd.
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