Migration of Langerhans cells in an in vitro organ culture system: IL-6 and TNF-alpha are partially responsible for migration into the epidermis

Although it is well established that epidermal Langerhans cells (LC) origin ate from bone marrow, little is known about the mechanism of this migration into the epidermis from bone marrow. In order to clarify the mechanism of this migration, we constructed an in vitro model. LC were depleted by daily topical application of clobetazole propionate (CP) solution onto the ear o f Balb/c mice. Seven days later, ear skin was cut off, separated and co-cul tured dermal-side-up with syngeneic (Balbjc), semisyngeneic ((C3H x Balb/c) F1), or allogeneic (C3H) epidermal cells (EC) for 3 days. We found (1) that a marked migration of donor LC into the recipient epidermis was observed i n the LC-depleted skin, (2) that only syngeneic LC actively migrated into t he recipient epidermis; however, the migration of semisyngeneic and allogen eic LC was detected at very low levels, (3) that the migratory capacity of donor LC was directly proved by a biolabeling technique using donor EC labe led with PKH-26, and (4) that anti-IL-6 and anti-TNF-cr antibodies inhibite d the migration of donor LC into the recipient epidermis. These data demons trate that the resident LC have the potential to traffic through the dermis into the epidermis in a highly syngeneic-specific fashion, and that IL-6 a nd TNF-alpha are partially responsible for promoting this migration. (C) 19 99 Elsevier Science Ireland Ltd. All rights reserved.