Imbalanced IL-1B and IL-18 Expression in Sezary Syndrome

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Manfrere, Kelly Cristina Gomes ; Torrealba, Marina Passos ; Ferreira, Frederico Moraes ; de Sousa, Emanuella Sarmento Alho ; Miyashiro, Denis ; Teixeira, Franciane Mouradian Emidio ; Custodio, Ricardo Wesley Alberca ; Nakaya, Helder I. ; Ramos, Yasmin Alefe Leuzzi ; Sotto, Mirian Nacagami ; Woetmann, Anders ; odum, Niels ; Duarte, Alberto Jose da Silva ; Sanches, Jose Antonio ; Sato, Maria Notomi

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 5, p. 13-pg., 2023-03-01.

Abstract

Sezary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3, whereas the pathway analysis indicated a further downregulation of IL1B-associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sezary syndrome. (AU)

• FAPESP's process: 20/02190-5 - Evaluation of inflammasome and microRNAs related to inflammation in Sézary Syndrome
• Grantee: José Antonio Sanches Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/25119-7 - Maternal-fetal interface: immunopathogenesis and vaccinal intervention in viral infections
• Grantee: Maria Notomi Sato
• Support Opportunities: Research Projects - Thematic Grants