Personal reflections on 25 years of immunodermatology

When I was invited by the British Association of Dermatologists to give the Rook Oration in 1999, the field of immunodermatology was enjoying a time of rapid evolution. We had just solved the structure of human cutaneous lymphocyte antigen (CLA) 2 years previously,1 and we were hard at work characterizing how the backbone of this structure, P selectin glycoprotein ligand‐1, was glycosylated by T cells destined to home to skin. My work over the previous 15 years had been focused on the production of cytokines by epidermal keratinocytes,2 3 4 5 6 culminating in the construction of transgenic mice that overexpressed cytokines under the control of keratin promoters,7 8 9 10 11 12 demonstrating that in vivo, keratinocyte cytokines could mediate inflammation and leucocyte recruitment. In the early 1980s, keratinocytes were still regarded as little more than the complex bricks and mortar of the epidermis, maintaining the barrier function of skin. Over the next decade it became clear that these cells could also participate in immune and inflammatory responses by elaborating cytokines, then a revolutionary idea.4 That an ‘activated epidermis’ could elaborate factors that would recruit leucocytes had never been previously considered, as Langerhans cells were thought to be the principal immunologically important cells in this tissue.13 We learned over the following years that keratinocyte cytokines could also influence the behaviour of dendritic cells, particularly as they efficiently present antigen to T cells.10 By the late 1990s, the participation of keratinocytes and other ‘innate immune’ cells in skin immunity had become accepted.6