Systemic and Local Increase of Granulysin Expression in Cytotoxic Lymphocytes in Severe Psoriasis
Marijana Vičić, Marija Kaštelan, Vlatka Sotošek Tokmadžić, Larisa Prpić Massari
Psoriasis is considered to be a cytokine-driven immune-mediated disease, although the cell cytotoxicity mechanisms involved remain unrecognized. Herein, we analyzed granulysin expression in different lymphocyte subsets of peripheral blood of 40 psoriatic patients (20 with severe and 20 with mild psoriasis) and seven sample of psoriatic skin. The simultaneous detection of intracellular granulysin and cell surface antigens was performed using flow cytometry in peripheral blood and immunohistochemistry in skin lesions. The frequency of granulysin+ cells, mean fluorescence intensity for granulysin, and the frequency of CD8+ T lymphocytes, NK cells, and NKT cells expressing granulysin molecules in peripheral blood were significantly higher in patients with severe psoriasis compared to mild disease and healthy individuals. These were also correlated with disease severity. Furthermore, granulysin+ cells, CD8+granulysin+ T lymphocytes, and CD56+granulysin+ NK cells were present in a higher frequency in the epidermal basal cell layer and in the dermal infiltrate of lesional skin as compared to non-lesional and healthy skin. In conclusion, granulysin+ cytotoxic cells are upregulated in blood and lesions of patients with psoriasis suggesting the involvement of granulysin mediated cytotoxicity in psoriasis pathogenesis.
Psoriasis is a chronic skin disease that affects 2% of the population. Apart from skin symptoms, patients may have psoriatic arthritis and other comorbidities, which can result in grave functional and emotional consequences. Finding a reason for psoriatic plaque formation is the major goal in recent psoriasis investigations. We demonstrated a possible involvement of cytotoxic molecule granulysin in psoriasis pathogenesis. Granulysin is highly expressed in peripheral blood and skin lesions of psoriatic patients in severe form of disease. Resolving the role of this molecule in psoriasis could be a possible way for creating a new target for novel antipsoriatic drug.