TY - JOUR
T1 - Imbalanced IL-1B and IL-18 Expression in Sézary Syndrome
AU - Manfrere, Kelly Cristina Gomes
AU - Torrealba, Marina Passos
AU - Ferreira, Frederico Moraes
AU - de Sousa, Emanuella Sarmento Alho
AU - Miyashiro, Denis
AU - Teixeira, Franciane Mouradian Emidio
AU - Custódio, Ricardo Wesley Alberca
AU - Nakaya, Helder I.
AU - Ramos, Yasmin Alefe Leuzzi
AU - Sotto, Mirian Nacagami
AU - Woetmann, Anders
AU - Ødum, Niels
AU - Duarte, Alberto José da Silva
AU - Sanches, José Antonio
AU - Sato, Maria Notomi
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023
Y1 - 2023
N2 - Sézary 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 Sézary syndrome.
AB - Sézary 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 Sézary syndrome.
KW - erythroderma skin
KW - IL-18
KW - IL-1B
KW - inflammasome
KW - lymph nodes
KW - Sézary syndrome
U2 - 10.3390/ijms24054674
DO - 10.3390/ijms24054674
M3 - Journal article
C2 - 36902104
AN - SCOPUS:85149915925
VL - 24
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
SN - 1661-6596
IS - 5
M1 - 4674
ER -