Immunopathology of atopic dermatitis

DYM Leung - Springer seminars in immunopathology, 1992 - Springer
DYM Leung
Springer seminars in immunopathology, 1992Springer
Conclusions In summary, AD is a chronic inflammatory skin disease associated with
increased IgE production, eosinophilia, increased mast cell number and increased
expression of the CD23 low-affinity IgE receptor on mononuclear cells. The basis of these
immunologic defects appear to be the result of increased numbers of IL-4-, IL-5-producing T
h 2 cells. This results in an overstimulation of their IL-4-IL-4 receptor pathway that is
accompanied by a relative deficiency of IFN-γ production. The acute manifestations of AD …
Conclusions
In summary, AD is a chronic inflammatory skin disease associated with increased IgE production, eosinophilia, increased mast cell number and increased expression of the CD23 low-affinity IgE receptor on mononuclear cells. The basis of these immunologic defects appear to be the result of increased numbers of IL-4-, IL-5-producing Th2 cells. This results in an overstimulation of their IL-4-IL-4 receptor pathway that is accompanied by a relative deficiency of IFN-γ production.
The acute manifestations of AD occur as the result of mast cell degranulation that can be triggered by a variety of stimuli including allergens, bacterial toxins or histamine-releasing factors secreted by activated T cells and macrophages. Mast cells release not only histamine which contributes to the acute sensation of pruritus but also cytokines and chemotactic factors which induce leukocyte adhesion molecules and attract inflammatory cells into the local tissue sites [3, 8, 26, 34].
The chronic manifestations of AD are probably the result of sustained cellular activation. The cellular infiltrate in the chronic lesion of AD consists primarily of T cells and macrophages [29]. T lymphocytes play two important roles in allergic responses: First, as already discussed they play a critical role in the regulation of IgE responses. Second, there is increasing evidence that they may play an important role in the control of the inflammatory response. This is orchestrated through organization of the cellular composition of the inflammatory cell infiltrate by the release of various cytokines. The release of IL-3, IL-5, and GM-CSF have pronounced effects on the differentiation and activation of eosinophils [52]. IL-3 promotes the growth of mucosal mast cells and stimulates basophil and mast cell histamine release. IL-4 promotes the growth of murine mast cells [18] and induces the expression of CD23 on macrophages [71]. The release of cytokines may, thus, account for the observation of increased mast cell number in chronic eczematoid lesions.
Taken together, these observations suggest that the AD skin lesion is characterized by the infiltration of inflammatory cells which differ from those infiltrating into a type IV contact-sensitivity reaction. The sustained immune activation, which results in chronic AD, may be the result of an underlying T cell defect, e.g., decreased IFN-γ production following the activation of lymphocytes with a variety of stimuli. Treatment of patients withh rIFN-γ down-regulates the IL-4-IL-4 receptor pathway which is overstimulated in this disease. It is important to note, however, that although many immunopathologic features of AD have recently been elucidated, the fundamental etiology of these abnormalities remains to be unraveled.
Springer