Evaluation of inflammasome and microRNAs related to inflammation in Sézary Syndrome

Abstract

The cutaneous T-cell lymphoma (LCCT), non-Hodgkin lymphoma, has a more aggressive form: the Sézary Syndrome (SS). The malignant cells are the lymphocyte TCD4+, present in the peripheral circulation, skin, lymph nodes, and in some cases, viscera. An important immunological dysfunction occurs in SS patients, which contributes to the morbidity and mortality of the disease. The skin of SS patients is commonly erythrodermic, favoring infections by cutaneous bacterias, which represents a characterized pattern in SS. Chronic inflammation can contribute to the development and progress of several types of cancer, therefore it is important to verify to ascertain the innate immune response, especially inflammasomes. In lymph nodes, few studies investigated the issue of innate immunity in SS patients, with an emphasis on the components of the inflammasome, especially the crosstalk between the inflammasomes and the profile of microRNAs (miRs) involved in the inflammatory response. Therefore, the aim of this study is to analyze the inflammasomes NLRP1, NRLP3, AIM2, and the cytokines IL-1² and IL-18 in the skin and lymph nodes of SS patients. In addition, evaluate the expression of miRs in lymph nodes cells: tumoral or non-tumoral. For this purpose, the expression of inflammasome markers in the skin of SS patients will be compared with LCCT non-erythrodermic (mycosis fungoides) in the patches and plaques stage. The miRs expression profile will be related to immune regulation and inflammation trough RNAs sequencing of the lymph nodes of SS patients. The miRS with potential therapeutic functional will be evaluated, via mimetics miRs, in a cell line of Sezary cells for inflammation regulation and cell proliferation. The search for miRs with potential therapeutic action, capable of regulating the inflamassome, inflammatory cytokine profile, or regulate immune response, will be valuable for the development of a new therapeutic intervention for the Sezary Syndrome. (AU)