Interleukin‐32 promotes detachment and activation of human Langerhans cells in a human skin explant model

J Gonnet, H Perrin, AJ Hutton, D Boccara… - British Journal of …, 2018 - academic.oup.com
J Gonnet, H Perrin, AJ Hutton, D Boccara, O Bonduelle, M Mimoun, M Atlan, A Soria…
British Journal of Dermatology, 2018academic.oup.com
Background Cross‐talk between skin keratinocytes (KCs) and Langerhans cells (LCs) 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 KCs on
surrounding LCs. Methods We used an ex vivo human explant model from healthy donors …
Background
Cross‐talk between skin keratinocytes (KCs) and Langerhans cells (LCs) 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 KCs on surrounding LCs.
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 KCs induced modest but significant morphological changes in LCs and downregulation of adhesion molecules, such as epithelial cell adhesion molecule and very late antigen‐4, and CXCL10 production. The treatment of KCs with IL‐32‐specific siRNA, 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 KCs, which initiated LC activation.
Conclusions
We propose, for the first time, that IL‐32 is a molecular link between KCs and LCs in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes.
Oxford University Press