Reactivity of resident immunocytes in normal and prepsoriatic skin using an ex vivo skin-explant model system.
BACKGROUND
While it is well known that both exogenous and endogenous stimuli can trigger appearance of psoriatic lesions, the initial cellular and molecular events mediated by immunocompetent cells normally resident in prepsoriatic (PN) skin are not well understood. Moreover, it is unclear whether there are any fundamentally important differences in the innate immune response of normal healthy skin (NN skin) versus PN skin. Since acute tissue responses to stimuli involve both resident cells and immunocytes recruited rapidly from circulation, it is difficult to discern the contribution of endogenous cells normally present in skin.


OBJECTIVE
To solely characterize the reactivity of resident immunocytes using an experimental system.


METHODS
To probe the activation potential of resident immunocytes in NN (n = 18) and PN skin (n = 10), a short-term ex vivo organ culture system containing interleukin (IL)-2 was established and characterized. To mimic exogenous or environmental trigger factors, bacteria-derived superantigens and lipopolysaccharide were added to the skin-explant assays, whereas endogenous trigger factors were investigated using heat shock proteins.


RESULTS
Using this skin-explant assay, both NN and PN skin gave rise to an expansion of various T-cell subsets, which could differentially produce various cytokines and a growth factor (keratinocyte growth factor), depending on the stimulus and source of skin. Bacterial superantigens were relatively potent inducers of interferon-gamma, and natural killer-T cells were observed proliferating from PN skin.


CONCLUSIONS
Despite relatively few T cells normally residing in either NN or PN skin, initiation of skin explants from both sets of individuals in the presence of IL-2 triggered vigorous T-cell proliferation and cytokine/growth factor release. These results demonstrate the utility of this skin-explant assay system to further investigate quantitative and qualitative immune responses of NN and PN skin.
Curry
Jonathan L
JL
Department of Pathology, Loyola University, Chicago Medical Center, Maywood, IL, USA.
Qin
Jian-Zhong
JZ
Robinson
June
J
Nickoloff
Brian J
BJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism; D006133:Growth Substances / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D016130:Immunophenotyping / Q000379:methods; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000737:chemistry / Q000502:physiology; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000502:physiology; D008875:Middle Aged; D009924:Organ Culture Techniques; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000166:cytology* / Q000276:immunology / Q000473:pathology*; D018089:Superantigens / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D003470:Culture Media; D016207:Cytokines; D004768:Enterotoxins; D006133:Growth Substances; D007376:Interleukin-2; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; C034959:enterotoxin C, staphylococcal