DERMATOLOGY EXPRESS REPORT™

Based on Data Presented at a Satellite Symposium held during the 67th Annual Meeting

Publication date: 2006-07-31

Mechanisms of Human Skin Immune Reactions: Cellular and Cytokine Components of the Dermal Immune System

This report was reviewed for medical and scientific accuracy by Amy S. Paller, MD, Walter J. Hamlin Professor and Chair, Department of Dermatology; Professor, Department of Pediatrics, The Feinberg School of Medicine, Northwestern University; Chicago, Illinois

Expert Commentary

Brian J. Nickoloff, MD, PhD, Professor and Associate Chairman of Pathology; Director, Oncology Institute; Deputy Director, Cardinal Bernardin Cancer Center; Director, Skin Disease Research Program; Loyola University of Chicago Medical Center; Maywood, Illinois

Historically, dermatology has led the investigative effort to identify and understand the molecular and cellular mechanisms of the human inflammatory response. Over the past several decades, significant progress has been made toward identifying and characterizing the mechanisms responsible for induction and resolution of inflammation. Regulation of inflammation involves positive and negative pathways. For example, in the presence of pathogens, the host-immune response and the acute inflammatory response serve a “helpful” purpose. Pathogens are removed as tissue repair is stimulated; tissue function is restored. When the regulation of the acute inflammatory response is altered, chronic inflammation and tissue dysfunction are “hurtful”; inflammation can lead to disease pathology. Evidence clearly demonstrates that skin diseases, such as psoriasis and atopic dermatitis, are characterized by chronic inflammation that contributes to altered barrier function, scale formation, and other detrimental consequences that require therapeutic intervention by dermatologists.

The history of investigation into the inflammatory response is an interesting one. In 1927, Sir Thomas Lewis elucidated the “triple response of skin” to a cutaneous injury - flush (redline), flare (red zone), and wheal (edema).¹ Lewis could eliminate the flare, but not the other components of the inflammatory response, by eliminating the autonomic nerve supply and preventing the “axon reflex.” This seminal work led to the eventual discovery of histamine, an important mediator in the inflammatory response. Myriad investigators followed Sir Lewis's lead and conducted complementary work that revealed further insights into the molecular and cellular mechanisms and mediators of inflammation. In the 1940s, Landsteiner and Chase established that a delayed hypersensitivity response was mediated by the cellular not the humoral arm of the immune system. ² More recently, advancements have been made in genetics, the immunological synapse, the untangling of the cytokine web and signaling pathways, xenotransplantation models, and the growing use of selectively targeted therapies for treating chronic and excessive inflammation disease states, such as psoriasis. ³

The complexities underlying the regulation of inflammation continue to evolve. At a recent CME-certified satellite symposium held during the 67th Annual Meeting of the Society for Investigative Dermatology in May 2006, leading researchers presented new insights on the mechanisms involved with initiation and resolution of inflammation. The presentations demonstrated that both initiation and resolution of inflammation represent highly regulated and active processes. Topics of discussion included initiation and resolution of acute inflammation; ⁴ tuning of inflammation by cytokines and decoy receptors; ⁵ a cellular perspective on the regulation of T-cell-mediated immune responses by antigen-presenting cells (APCs) that express indoleamine 2,3-dioxygenase (IDO); ⁶ the role of regulatory T cells in modulating immune responses; ⁷ and a clinical perspective on approaches to unanswered questions whose answers could suggest a means to dampening the inflammatory response. ⁸

This Dermatology Express Report^TM reviews the important concepts discussed during these presentations to provide a thorough appreciation of the complex interplay of mediators and cells that c