Contact allergens and epidermal proinflammatory cytokines modulate Langerhans cell E-cadherin expression in situ.
After exposure to antigen, Langerhans cells (LC) migrate from the epidermis to lymph nodes, where they initiate primary immune responses in T cells. The adhesion molecule E-cadherin mediates adhesion of LC to keratinocytes in vitro and may be responsible for localization of LC in epidermis. To determine if levels of LC E-cadherin are modulated during LC emigration from epidermis, we utilized flow cytometry to evaluate E-cadherin expression on BALB/c LC exposed in situ to the contact allergen 2,4,6-trinitrochlorobenzene (TNCB). TNCB induced increased I-A/E antigen and decreased E-cadherin expression on a subpopulation of LC as early as 12 h, and as late as 48 h, after application. At 24 h, approximately 30% of LC in TNCB-treated skin expressed increased I-A/E antigens; of these activated LC, approximately 40% expressed decreased levels of E-cadherin. E-cadherin levels on this latter subset were approximately 15% of those expressed by LC in normal skin, and were similar to levels on cultured LC and LC that migrated from skin explants. The effect was specific for allergens; no changes occurred in LC following treatment with several contact irritants or the tolerogen dinitrothiocyanobenzene. To determine if cytokines modulated LC E-cadherin expression, we introduced various cytokines into BALB/c ear skin and assayed I-A/E antigen and E-cadherin levels. Of the cytokines tested, only interleukin-1 and tumor necrosis factor alpha reproduced the effects of TNCB. We propose that downmodulation of E-cadherin expression occurs as a consequence of local cytokine production during antigen-induced LC activation, facilitating LC emigration and the initiation of immune responses against antigens encountered in epidermis.
Schwarzenberger
K
K
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, U.S.A.
Udey
M C
MC
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D004817:Epidermis / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009578:Nitrobenzenes / Q000276:immunology / Q000494:pharmacology; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000485:Allergens; D015820:Cadherins; D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D009578:Nitrobenzenes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C019567:tetrachloronitrobenzene; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor