B7-1 expression of Langerhans cells is up-regulated by proinflammatory cytokines, and is down-regulated by interferon-gamma or by interleukin-10.
Langerhans cells (LC) act as potent antigen-presenting cells (APC) for primary and secondary T cell-dependent immune responses. LC express several costimulatory and/or adhesion molecules such as B7/BB1, which has been implicated as one of the important determinants for professional APC. Recent studies have shown that B7/BB1 antigens comprise three distinct molecules termed B7-1, B7-2, and B7-3. We have examined the regulatory properties of B7-1 expression in LC using various cytokines including interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, interferon (IFN)-gamma, granulocyte/macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-alpha. We have demonstrated: 1) that the B7-1 expression of LC is reproducibly up-regulated by either GM-CSF, TNF-alpha, IL-1 alpha, IL-1 beta, or IL-4 in a dose- and time-dependent manner, 2) that GM-CSF exhibits the most active effect on B7-1 up-regulation in each experiment, 3) that IFN-gamma or IL-10 profoundly inhibits the B7-1 expression of LC in a dose- and time-dependent manner, and 4) that the down-regulatory ability of IFN-gamma or IL-10 neutralizes the activity of up-regulatory cytokines. The enhancing or inhibitory action of these cytokines on B7-1 expression occurs selectively because none of the cytokines consistently affects I-A expression of LC. These data suggest that the B7-1 expression of LC may be dynamically regulated by these up- and down-regulatory cytokines in normal and inflammatory epidermal microenvironment.
Chang
C H
CH
Department of Dermatology, Yamanashi Medical University, Japan.
Furue
M
M
Tamaki
K
K
D000818:Animals; D018122:B7-1 Antigen / Q000032:analysis*; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology*; D007801:Langerhans Cells / Q000737:chemistry*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000494:pharmacology
D018122:B7-1 Antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma