Epidermal cytokine and neuronal peptide modulation of contact hypersensitivity reactions

Cellular and molecular mechanisms underlying contact hypersensitivity reactions have been, and still are, fields under intense investigation, not only for the importance of these reactions in clinical medicine, but also because they are considered prototypic of a vast group of T cell-mediated immune diseases of the skin. Interestingly, potent contributions by non-bone marrow-derived cells have been shown clearly, demonstrating that epidermal cells are far more than mere spectators of these reactions, and undergo a functional activation after contact with the hapten causing the hypersensitivity reaction. In particular, keratinocyte contribution to the onset as well as modulation of contact hypersensitivity reactions through the release of a plethora of cytokines, has been widely documented. Moreover, an important control over these reactions is exerted by local release of neuropeptides by nerve endings. This review paper focuses on epidermal cytokine and neuronal peptide modulation of contact hypersensitivity reactions, trying to document the complexity of the regulatory systems, active during these immune processes of the skin.