Interleukin-1 from epithelial cells fosters T cell-dependent skin inflammation.
BACKGROUND
Chronic inflammatory skin diseases such as atopic dermatitis and psoriasis are characterized by the infiltration of lymphocytes into the epidermal compartment. Several studies point to an active role of skin epithelial cells in the pathophysiology of such diseases.


OBJECTIVE
In this study we addressed the regulatory function of primary human keratinocytes in the interaction with autologous T cells and monocytes.


METHODS
We used a human coculture model with keratinocytes grown from epidermal stem cells of the outer root sheath of human hair follicles and autologous T cells.


RESULTS
In our coculture system we observed a high production of interferon (IFN)-γ, but not Th2 cytokines, in the presence of superantigen or antigen-pulsed autologous monocytes. Critical parameters for this effect were: (i) T-cell receptor activation, (ii) an intercellular adhesion molecule-1/lymphocyte function-associated antigen (LFA)-1-dependent interaction between keratinocytes and T cells, and (iii) secretion of interleukin (IL)-1β. Remarkably, in the presence of activated T cells, epithelial cells seemed to be a more significant source of IL-1β than monocytes. Application of the LFA-1 blocker efalizumab or IL-1 receptor antagonist anakinra enabled us to suppress completely the production of IFN-γ by T cells in the coculture.


CONCLUSIONS
IL-1 secretion and the physical contact between keratinocytes and activated, infiltrating T cells may be central for the development of chronic inflammatory skin conditions.
Department of Dermatology, Hannover Medical School, Ricklinger Str. 5, D-30449 Hannover, Germany. renne.julius@mh-hannover.de
J
J
Renne
V
V
Schäfer
T
T
Werfel
M
M
Wittmann
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000494:pharmacology; D002450:Cell Communication; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology / Q000502:physiology*; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D016207:Cytokines; D007155:Immunologic Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007371:Interferon-gamma; C472181:efalizumab