Acta Dermato-Venereologica 99-12CompleteContent

1136 INVESTIGATIVE REPORT Systemic and Local Increase of Granulysin Expression in Cytotoxic Lymphocytes in Severe Psoriasis Marijana VIČIĆ 1 , Marija KAŠTELAN 1 , Vlatka SOTOŠEK TOKMADŽIĆ 2 and Larisa PRPIĆ MASSARI 1 1 Department of Dermatovenereology, and 2 Department of Anesthesia, Resuscitation and Intensive Care, Medical Faculty University of Rijeka, Clinical Hospital Center Rijeka, Rijeka, Croatia Psoriasis is considered to be a cytokine-driven immu- ne-mediated disease, although the cell cytotoxicity mechanisms involved remain unrecognized. Here in, 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 pe- ripheral blood and immunohistochemistry in skin le- sions. The frequency of granulysin + cells, mean fluore scence intensity for granulysin, and the frequency of CD8 + T lymphocytes, NK cells, and NKT cells expressing granulysin molecules in peripheral blood were signi- ficantly higher in patients with severe psoriasis com- pared to mild disease and healthy individuals. These were also correlated with disease severity. Further- more, granulysin + cells, CD8 + granulysin + T lymphocy- tes, 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, granu lysin + cytotoxic cells are upregulated in blood and le- sions of patients with psoriasis suggesting the involve- ment of granulysin mediated cytotoxicity in psoriasis pathogenesis. Key words: cytotoxicity; granulysin; psoriasis; T lymphocytes. Accepted Aug 22, 2019; E-published Aug 22, 2019 Acta Derm Venereol 2019; 99: 1136–1142. Corr: Larisa Prpić Massari, MD, PhD, Department of Dermatovenereo- logy, Medical Faculty University of Rijeka, Clinical Hospital Centre Rijeka, Krešimirova 42, HR-51000 Rijeka, Croatia. E-mail: larisa.prpic@medri. uniri.hr P soriasis is a chronic inflammatory skin disease that affects around 2% of the population (1). Although the disease may present with different clinical features, the most common presentation is the vulgar form, cha- racterized by erythematosquamous plaques covering the elbows, knees, lumbosacral area, or in more severe cases, even larger body surfaces (2). Although the exact mechanism of skin lesion development remains unclear, psoriasis is generally perceived as an inflammatory cell- mediated skin disease (3). The most common inflam- matory cells in the peripheral blood, skin, and joints are T lymphocytes, but the significance of dendritic cells doi: 10.2340/00015555-3298 Acta Derm Venereol 2019; 99: 1136–1142 SIGNIFICANCE 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 re- sult in grave functional and emotional consequences. Fin- ding 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 se- vere 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. (DCs), macrophages, natural killer (NK) cells, and na- tural killer T (NKT) cells has also been confirmed (4). Two main cytotoxic lymphocyte subsets, CD8 + T cells and NK cells, are capable of inducing target cell death by releasing cytotoxic armamentarium, such as perforin, granzyme B, and granulysin (GNLY) (5). The upregula- tion of perforin and granzyme B in the peripheral blood and lesional skin of psoriasis patients has been previously demonstrated (6–8). The presence of GNLY was only recently detected in psoriatic lesions. However, its spe- cific involvement and role in psoriasis pathogenesis is still unclear (9, 10). GNLY is a cytotoxic molecule with lytic properties expressed in activated T, NK, and NKT cells (11, 12). The cytotoxic effects of GNLY on tumor cells and cells infected by a variety of microorganisms have been confirmed (11, 12). However, GNLY also serves as a chemoattractant for T lymphocytes, monocytes, and NK cells, in addition to attracting and activating DCs (11). In our previous studies, we have demonstrated upre- gulation of perforin molecule in peripheral blood of severe psoriasis mainly in the cytotoxic cell subtypes such as CD4 + T lymphocytes, CD8 + T lymphocytes and NK cells (8, 13). We have also found an increase of perforin positive cells in epidermis of psoriasis lesions (7). We suggested an involvement of perforin-mediated cytotoxicity in psoriasis pathogenesis. Herein, we hypothesized that GNLY expression profi- les would play an important role in disease pathogenesis. Consequently, we examined the dynamics of systemic GNLY expression in peripheral blood lymphocytes This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.

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