TY - JOUR
T1 - Contact allergens and epidermal proinflammatory cytokines modulate Langerhans cell E-cadherin expression in situ
AU - Schwarzenberger, Kathryn
AU - Udey, Mark C.
PY - 1996
Y1 - 1996
N2 - 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 how 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, ~ 30% of LC in TNCB-treated skin expressed increased I-A/E antigens; of these activated LC, ~ 40% expressed decreased levels of E-cadherin. E-cadherin levels on this latter subset were ~ 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 dinitrathiocyanobenzene. 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 a 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.
AB - 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 how 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, ~ 30% of LC in TNCB-treated skin expressed increased I-A/E antigens; of these activated LC, ~ 40% expressed decreased levels of E-cadherin. E-cadherin levels on this latter subset were ~ 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 dinitrathiocyanobenzene. 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 a 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.
KW - Activation
KW - Adhesion
KW - Leukocyte
KW - Migration
UR - http://www.scopus.com/inward/record.url?scp=0029984623&partnerID=8YFLogxK
U2 - 10.1111/1523-1747.ep12344019
DO - 10.1111/1523-1747.ep12344019
M3 - Article
C2 - 8648193
AN - SCOPUS:0029984623
SN - 0022-202X
VL - 106
SP - 553
EP - 558
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -