Skin Immunity

Experimental Dermatology 2006: 15: 913–929 Blackwell Munksgaard . Printed in Singapore doi: 10.1111/j.1600-0625.2006.506_01.x

Copyright Ó 2006 The Authors. Journal compilation Ó 2006 Blackwell Munksgaard

Experimental Dermatology
ISSN 0906-6705

Controversies in Experimental Dermatology ¨ Section Editor: Ralf Paus, Lubeck

Who is really in control of skin immunity under physiologicalcircumstances – lymphocytes, dendritic cells or keratinocytes?
Schroder JM, Reich K, Kabashima K, Liu FT, Romani N, Metz M, Kerstan A, ¨ Lee PHA, Loser K, Schon MP, Maurer M, Stoitzner P, Beissert S, Tokura Y, ¨ Gallo RL. Who is really in control of skin immunity under physiological circumstances – lymphocytes, dendritic cells or keratinocytes? Exp Dermatol 2006: 15: 913–929. Ó 2006 The Authors.Journal compilation Ó 2006 Blackwell Munksgaard. ¨ J. M. Schroder, K. Reich, K. Kabashima, F. T. Liu, N. Romani, M. Metz, A. Kerstan, P. H. A. Lee, K. Loser, ¨ M. P. Schon, M. Maurer, P. Stoitzner, S. Beissert, Y. Tokura and R. L. Gallo

Abstract: Our views of the skin immunity theatre are undergoing constant change. These not only reflect paradigm shifts in general immunology and skin biology, butalso have profound clinical implications, which call for strategic changes in dermatological therapy. Nowhere can this be witnessed at a greater level of instructiveness and fascination than when addressing the question posed by this new Controversies feature. Thus, after a very long period of dominance by T cells and Langerhans cells as ‘lead actors’ on the skin immunity stage, the lowlykeratinocyte has recently made an astounding theatrical appearance as a key protagonist of the innate skin immunity system, which may control even acquired skin immune responses. Further enhancing dramatic complexity and tension, the mast cell has entered as an additional actor claiming centre stage, and the epidermal Langerhans cell has slipped in a surprise appearance as the chief agent ofimmunotolerance. May you, esteemed reader, enjoy the spectacle offered here by selected immunodermatology authorities who double as ‘stage managers’ pushing their respective favourite actors into the limelight. You get everything you may expect from a good performance – complete with the impresario’s overture that lures you into the theatre and sets the stage, competing divas, recently discovered new talentsand even the critic’s digest while the performance is still ongoing. By the time the curtain drops, you will have reached your own, independent conclusions on how to answer the title question of this play – at least for the time being…

Prelude The trouble with working at an environmental interface
What is the main task of the skin immune system? The task is to defend a critical border. Theepidermis is a strong barrier. Covered by a three-dimensional self-sustaining brick wall of corneocytes embedded in a lipid-rich envelope, it consists of several layers of tightly connected keratinocytes. Keratinocyte cohesion is conferred by special structures, the desmosomes. Transmembranous des-

mosomal components of neighbouring cells, desmogleins and desmocollins, intercalate and form adhesivebridges. They are connected to intracellular molecules of the desmosomal plaques which in turn interact with components of the cytoskeleton (1). The dermoepidermal basement membrane zone is the inner sheath of our cutaneous wall. The epidermis protects us against mechanical, physical, biological and chemical injury. The epidermis can tan and sense. It can also defend itself to a certain degreebecause it is equipped with an evolutionary old, but effective system of primary defense

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which is referred to as innate immune system. But the real troops, the evolutionary younger, thymus-trained allrounders brim-full with multifunctional cytokines come in via dermal vessels. This is necessary because many things can go wrong. A plethora of potentially harmful...