Unpacking the complexity of nuclear IL-33 (nIL-33): a crucial regulator of transcription and signal transduction

Wang, Zengbin; Tang, Nanhong

doi:10.1007/s12079-023-00788-1

Cited by 4 publications

(4 citation statements)

References 97 publications

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“…Recent studies have begun to survey full-length IL-33 as a possible initiator of noncanonical, ST2-independent signaling, mostly examining its effects on epithelial cells and fibroblasts [58,59]. These noncanonical, ST2-independent signaling actions of full-length IL-33 have also been attributed to its function as a transcription regulator of the p65 subunit of the NF-κB complex [60,61]. Interestingly, a study from Hussey et al has indicated full-length IL-33 can direct macrophage differentiation towards a M2 phenotype [62], which studies have shown to be expanded during normal pregnancy and impaired during PE [63].…”

Section: Discussionmentioning

confidence: 99%

IL‐33 Signaling Inhibition Leads to a Preeclampsia‐Like Phenotype in Pregnant Rats

Wang,

Shields,

Thompson

et al. 2024

American J Rep Immunol

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ProblemPreeclampsia (PE) is a hypertensive pregnancy disorder that is a leading cause of maternal and fetal morbidity and mortality characterized by maternal vascular dysfunction, oxidative stress, chronic immune activation, and excessive inflammation. No cure exists beyond delivery of the fetal–placental unit and the mechanisms driving pathophysiology are not fully understood. However, aberrant immune responses have been extensively characterized in clinical studies and shown to mediate PE pathophysiology in animal studies. One pathway that may mediate aberrant immune responses in PE is deficiencies in the IL‐33 signaling pathway. In this study, we aim to investigate the impact of IL‐33 signaling inhibition on cNK, TH17, and TReg populations, vascular function, and maternal blood pressure during pregnancy.Method of StudyIn this study, IL‐33 signaling was inhibited using two different methods: intraperitoneal administration of recombinant ST2 (which acts as a decoy receptor for IL‐33) and administration of a specific IL‐33 neutralizing antibody. Maternal blood pressure, uterine artery resistance index, renal and placental oxidative stress, cNK, TH17, and TReg populations, various cytokines, and pre‐proendothelin‐1 levels were measured.ResultsIL‐33 signaling inhibition increased maternal blood pressure, uterine artery resistance, placental and renal oxidative stress. IL‐33 signaling inhibition also increased placental cNK and TH17 and renal TH17 cells while decreasing placental TReg populations. IL‐33 neutralization increased circulating cNK and TH17s and decreased circulating TRegs in addition to increasing pre‐proendothelin‐1 levels.ConclusionsData presented in this study demonstrate a role for IL‐33 signaling in controlling vascular function and maternal blood pressure during pregnancy possibly by mediating innate and adaptive immune inflammatory responses, identifying the IL‐33 signaling pathway as a potential therapeutic target for managing preeclampsia.

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Section: Discussionmentioning

confidence: 99%

IL‐33 Signaling Inhibition Leads to a Preeclampsia‐Like Phenotype in Pregnant Rats

Wang,

Shields,

Thompson

et al. 2024

American J Rep Immunol

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“…IL-33 plays a protective role against parasites by promoting the recruitment, amplification, and maturation of neutrophils and eosinophils. It can exist in three forms: full-length IL-33 (FLIL-33), secreted soluble cytokine IL-33 (sIL-33), and nuclear IL-33 (nIL-33), with different implications in tumor immunity that can vary depending on the tumor histotype [22][23][24].…”

Section: Il-1 Family Cytokinesmentioning

confidence: 99%

IL-1 Family Members in Bone Sarcomas

Landuzzi,

Ruzzi,

Pellegrini

et al. 2024

Cells

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IL-1 family members have multiple pleiotropic functions affecting various tissues and cells, including the regulation of the immune response, hematopoietic homeostasis, bone remodeling, neuronal physiology, and synaptic plasticity. Many of these activities are involved in various pathological processes and immunological disorders, including tumor initiation and progression. Indeed, IL-1 family members have been described to contribute to shaping the tumor microenvironment (TME), determining immune evasion and drug resistance, and to sustain tumor aggressiveness and metastasis. This review addresses the role of IL-1 family members in bone sarcomas, particularly the highly metastatic osteosarcoma (OS) and Ewing sarcoma (EWS), and discusses the IL-1-family-related mechanisms that play a role in bone metastasis development. We also consider the therapeutic implications of targeting IL-1 family members, which have been proposed as (i) relevant targets for anti-tumor and anti-metastatic drugs; (ii) immune checkpoints for immune suppression; and (iii) potential antigens for immunotherapy.

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“…Interleukin 33 (IL-33), initially identified as a nuclear factor in high endothelial venules (NF-HEV) (1), is structurally related to the cytokines of the IL-1 family and it is expressed by fibroblasts, endothelial and epithelial cells, among other cell types (2). The full-length human IL-33 precursor encompasses 270 amino acids, featuring an N-terminal region that includes a chromatin binding motif and a nuclear localization signal (amino acids 1-65), a sensor domain from amino acid 66 to 111, and a C-terminal IL-1-like cytokine domain (amino acids 112-270) that gives IL-33 its cytokine-like properties (3).…”

Section: Introductionmentioning

confidence: 99%

“…The full-length IL-33 molecule of 33 kDa can be found in the nucleus and retained there (1). When cellular injury occurs, IL-33 is released and processed to a mature form by protease cleavage (2). The mature form of IL-33 has a high affinity to the ST2 receptor.…”

Section: Introductionmentioning

confidence: 99%

Unveiling the multifaceted antitumor effects of interleukin 33

Arrizabalaga,

Risson,

Ezcurra-Hualde

et al. 2024

Front. Immunol.

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Interleukin 33 (IL-33), once predominantly recognized for its pro-tumoral activities, has emerged as a multifunctional cytokine with antitumor properties. IL-33 pleiotropic activities include activation of Th1 CD4+ T cells, CD8+ T cells, NK cells, dendritic cells, eosinophils, as well as type 2 innate lymphoid cells. Regarding this immunomodulatory activity, IL-33 demonstrates synergistic interactions with various cancer therapies, including immune checkpoint blockade and chemotherapy. Combinatorial treatments leveraging IL-33 exhibit enhanced antitumor efficacy across different tumor models, promising novel avenues for cancer therapy. Despite its antitumor effects, the complex interplay of IL-33 within the tumor microenvironment underscores the need for further investigation. Understanding the mechanisms underlying IL-33’s dual role as both a promoter and inhibitor of tumor progression is essential for refining therapeutic strategies and fully realizing its potential in cancer immunotherapy. This review delves into the intricate landscape of IL-33 effects within the tumor microenvironment, highlighting its pivotal role in orchestrating immune responses against cancer.

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Unpacking the complexity of nuclear IL-33 (nIL-33): a crucial regulator of transcription and signal transduction

Cited by 4 publications

References 97 publications

IL‐33 Signaling Inhibition Leads to a Preeclampsia‐Like Phenotype in Pregnant Rats

IL‐33 Signaling Inhibition Leads to a Preeclampsia‐Like Phenotype in Pregnant Rats

IL-1 Family Members in Bone Sarcomas

Unveiling the multifaceted antitumor effects of interleukin 33

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