Characteristics and regulation of the expression on interleukin 1 receptors by murine Langerhans cells and keratinocytes.
There is increasing evidence that interleukin 1beta (IL-1beta), a product in murine epidermis of Langerhans cells (LC) exclusively, contributes to the initiation and regulation of LC migration in response to skin sensitization. The hypothesis is that IL-1beta induces the production by keratinocytes of tumour necrosis factor alpha (TNF-alpha) which acts in a paracrine fashion on LC to provide one signal for migration. In addition, it is believed that IL-1beta acts in an autocrine fashion on LC to provide a second, TNF-alpha-independent, signal for the initiation of this response. The viability of this hypothesis is dependent upon the availability of appropriate membrane receptors. We describe therefore experiments designed to investigate the IL-1 receptor (IL-1R) status of keratinocytes, LC and lymph node dendritic cells (DC). Flow cytometric analyses of epidermal cell suspensions revealed at least 60% of LC positive for the type I IL-1R (IL-1RI). In contrast, only a small proportion of keratinocytes displayed surface IL-1RI, although high intracellular expression of this receptor could be detected either by flow cytometric analysis of cells permeabilized with saponin or by immunofluorescence microscopy. Expression of the type II IL-1R (IL-1RII) was detected at relatively low levels on both LC and keratinocytes. Interestingly, DC isolated from the lymph nodes of sensitized mice displayed upregulated expression of IL-1RI and lower levels of IL-1RII compared to LC. The conclusion drawn is that the IL-1R phenotype of LC and keratinocytes under resting conditions is consistent with the proposed contribution of IL-1beta to LC migration. Furthermore, the regulation of IL-1R expression by epidermal cells and DC will undoubtedly influence the development of cutaneous immune responses.
Cumberbatch
M
M
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK. marie.cumberbatch@ctl.zeneca.com
Dearman
R J
RJ
Kimber
I
I
D000818:Animals; D003713:Dendritic Cells / Q000737:chemistry; D015603:Keratinocytes / Q000737:chemistry*; D007801:Langerhans Cells / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D017472:Receptors, Interleukin-1 / Q000032:analysis*
D017472:Receptors, Interleukin-1