Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations.

Abstract

PerspectivesEpithelial tissues in general (and skin in particular) define boundaries between inside and outside, host and environment.Mammalian skin and its appendages are poised at the critical interface between the delicately balanced internal milieu ofthe host and the mercurial forces of the outside world.Human skin diseases characterized by histopathologically distinct pat- terns of infiltration by T cells, B cells, monocytes, and granu- locytes (referred to collectively as leukocytes) number quite literally in the hundreds.To state that the pathophysiologic mechanisms involved in the evolution of such unique inflam- matory infiltrates are poorly understood is to euphamize; yet, recent advances have begun to allow for the construction of hypothetical paradigms that address the issue of mechanism in cutaneous immune and inflammatory processes.While skin was once considered the inert canvas upon which immune and inflammatory processes were painted by the bone marrow-derived host defense system, it is becoming apparent that resident sessile cells of skin are perhaps no less important in the generation ofa cutaneous immune or inflam- matory response.This contention is based upon two broad classes of observation.The first is that nonhematopoieticallyderived cells resident to skin (including dermal fibroblasts, endothelial cells, and epidermal keratinocytes and melano- cytes) can produce various cytokines upon appropriate stimu- lation (reviewed in reference 1) that affect decisively the behav- ior and function of lymphocytes, granulocytes, and mono- cytes.The second class of observation is that several of these cytokines influence the expression of adhesion molecules on endothelial and epithelial cells (1, 2).Taken to their logical conclusions, these observations suggest that nonhematopoietically-derived cells of skin, by virtue of their potential for cyto- kine production, have the indirect capacity to trap appropriate classes of leukocytes within microvasculature at precise ana- tomical sites, guide them through vessel walls and through dermal tissue along chemotactic gradients, and then activate them in situ.This article will review some of the evidence for this special immunocompetence of the skin, especially with regard to newer observations relating to cytokine production. Cytokines in cutaneous tissuesIt is axiomatic that cells ofdistinct lineages must communicate during the successful localization and evolution of an inflam- matory response, and cytokines comprise an important part of