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Interleukin‐32 promotes detachment and activation of human Langerhans cells in a human skin explant model
Author(s) -
Gonnet J.,
Perrin H.,
Hutton A.J.,
Boccara D.,
Bonduelle O.,
Mimoun M.,
Atlan M.,
Soria A.,
Combadière B.
Publication year - 2018
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.16721
Subject(s) - proinflammatory cytokine , epidermis (zoology) , microbiology and biotechnology , langerhans cell , dermis , interleukin , cell adhesion molecule , cytokine , biology , immunology , chemistry , antigen , inflammation , anatomy
Summary Background Cross‐talk between skin keratinocytes ( KC s) and Langerhans cells ( LC s) plays a fundamental role in the body's first line of immunological defences. However, the mechanism behind the interaction between these two major epidermal cells is unknown. Interleukin ( IL )‐32 is produced in inflammatory skin disorders. We questioned the role of IL ‐32 in the epidermis. Objectives We aimed to determine the role of IL ‐32 produced by KC s on surrounding LC s. Methods We used an ex vivo human explant model from healthy donors and investigated the role of IL ‐32 on LC activation using imaging, flow cytometry, reverse transcriptase quantitative polymerase chain reaction and small interfering (si) RNA treatment. Results Modified vaccinia virus ankara ( MVA ) infection induced KC death alongside the early production of the proinflammatory cytokine IL ‐32. We demonstrated that IL ‐32 produced by MVA ‐infected KC s induced modest but significant morphological changes in LC s and downregulation of adhesion molecules, such as epithelial cell adhesion molecule and very late antigen‐4, and CXCL 10 production. The treatment of KC s with IL ‐32‐specific si RNA , and anti‐ IL ‐32 blocking antibody significantly inhibited LC activation, demonstrating the role of IL ‐32 in LC activation. We also found that some Toll‐like receptor ligands induced a very high level of IL ‐32 production by KC s, which initiated LC activation. Conclusions We propose, for the first time, that IL ‐32 is a molecular link between KC s and LC s in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes.