Full-length IL-33 regulates Smad3 phosphorylation and gene transcription in a distinctive AP2-dependent manner

Luzina, Irina G.; Fishelevich, Rita; Hampton, Brian; Courneya, Jean-Paul; Parisella, Francesca Romana; Lugkey, Katerina N.; Baleno, Frank X.; Choi, Dong Lak; Kopach, Pavel; Lockatell, Virginia; Todd, Nevins W.; Atamas, Sergei P.

doi:10.1016/j.cellimm.2020.104203

Cited by 9 publications

(6 citation statements)

References 47 publications

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“…In vivo overexpression of FLIL33 leads to a mild non-Th2 lymphocytic infiltration (Luzina et al 2013). Furthermore, FLIL33 is found to trigger the phosphorylation of Smad3, a critical profibrotic signaling mediator of TGF-β, in primary human lung fibroblasts (Luzina et al 2020).…”

Section: Flil33 and Pulmonary Fibrosismentioning

confidence: 99%

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

Wang,

Tang

2023

J. Cell Commun. Signal.

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Small ubiquitin-related modifier USP21 Ubiquitin-specific peptidase 21 SMAD3 Smad family member 3 TSLP Thymic Stromal Lymphopoietin hBD2 Human beta-defensin 2 GATA3 GATA-binding protein 3 HDACs Histone deacetylases PARP1 (ADP-ribose) polymerase 1 ATM Ataxia-telangiectasia mutated BER Base excision repair DSB DNA double-strand break DDR DNA damage response DDIT3 DNA damage-inducible transcript 3 TNF-α Tumor necrosis factor-α,SASP,senescenceassociated secretory phenotype PROTACs Proteolysis-targeting chimeras DUBTACs Deubiquitinase targeting chimeras TPS Targeted protein stabilization SENP2 SUMO specific protease 2 Nanhong Tang

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Section: Flil33 and Pulmonary Fibrosismentioning

confidence: 99%

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

Wang,

Tang

2023

J. Cell Commun. Signal.

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“…We and others have reported that IL-33 can exist as a full-length precursor (flIL-33), which is nearly exclusively a nuclear protein, [30][31][32][33] or as a proteolytically cleaved shorter mature forms (mIL-33) with progressive cleavage increasing activity. [33][34][35][36] Fulllength IL-33 does not engage surface cytokine receptors and is known to induce only mild lymphocytic and neutrophilic inflammation while the cleaved mature form signals through the canonical T1/ST-2 receptor with robust activity. 34 While we have previously described that resting human lungs contain substantial amounts of the full-length IL-33, 34,37 in the setting of brain death followed by preservation and cold storage in Perfadex® solution, as is customary post organ harvest, we were able to document an increase in the cleaved isoform which progressed post organ preservation noted no increase in IL-5 compared to resting lungs (Figure 6D), indicating that IL-33 is critical for the activation of lung-resident ILC2s by IRI.…”

Section: Il-33 Induced By Ischemia Reperfusion Injury Activates Donor...mentioning

confidence: 99%

“…To investigate the physiology of IL-33 in donor lungs, we next utilized human lung tissue obtained during the process of transplantation. We and others have reported that IL-33 can exist as a full-length precursor (flIL-33), which is nearly exclusively a nuclear protein, [30][31][32][33] or as a proteolytically cleaved shorter mature forms (mIL-33) with progressive cleavage increasing activity. [33][34][35][36] Fulllength IL-33 does not engage surface cytokine receptors and is known to induce only mild lymphocytic and neutrophilic inflammation while the cleaved mature form signals through the canonical T1/ST-2 receptor with robust activity.…”

Section: Il-33 Induced By Ischemia Reperfusion Injury Activates Donor...mentioning

confidence: 99%

Ischemia reperfusion injury facilitates lung allograft acceptance through IL-33-mediated activation of donor-derived IL-5 producing group 2 innate lymphoid cells

Guo

Mei

et al. 2022

American Journal of Transplantation

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Pathways regulating lung alloimmune responses differ from most other solid organs and remain poorly explored. Based on our recent work identifying the unique role of eosinophils in downregulating lung alloimmunity, we sought to define pathways contributing to eosinophil migration and homeostasis. Using a murine lung transplant model, we have uncovered that immunosuppression increases eosinophil infiltration into the allograft in an IL‐5‐dependent manner. IL‐5 production depends on immunosuppression‐mediated preservation of donor‐derived group 2 innate lymphoid cells (ILC2). We further describe that ischemia reperfusion injury upregulates the expression of IL‐33, which functions as the dominant and nonredundant mediator of IL‐5 production by graft‐resident ILC2. Our work thus identifies unique cellular mechanisms that contribute to lung allograft acceptance. Notably, ischemia reperfusion injury, widely considered to be solely deleterious to allograft survival, can also downregulate alloimmune responses by initiating unique pathways that promote IL‐33/IL‐5/eosinophil‐mediated tolerance.

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“…AP2B1, the other large β subunit of the AP2 subunit, shares common binding proteins with the α subunits. For example, both AP2B1 and AP2A1 bind to full-length IL-33 [ 93 ] and both were reported to be involved in common functions, such as synaptic vesicle cycle [ 9 , 68 , 94 ] and cell development [ 95 , 96 ]. Moreover, the pathological consequences of AP2B1 mutation are similar to those of the AP2α subunit mutation and has been shown to have various effects in neural tissue.…”

Section: Ap2 Complexmentioning

confidence: 99%

Role of adaptin protein complexes in intracellular trafficking and their impact on diseases

Shin

Nile

2021

Bioengineered

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Adaptin proteins (APs) play a crucial role in intracellular cell trafficking. The 'classical' role of APs is carried out by AP1-3, which bind to clathrin, cargo, and accessory proteins. Accordingly, AP1-3 are crucial for both vesicle formation and sorting. All APs consist of four subunits that are indispensable for their functions. In fact, based on studies using cells, model organism knockdown/knock-out, and human variants, each subunit plays crucial roles and contributes to the specificity of each AP. These studies also revealed that the sorting and intracellular trafficking function of AP can exert varying effects on pathology by controlling features such as cell development, signal transduction related to the apoptosis and proliferation pathways in cancer cells, organelle integrity, receptor presentation, and viral infection. Although the roles and functions of AP1-3 are relatively well studied, the functions of the less abundant and more recently identified APs, AP4 and AP5, are still to be investigated. Further studies on these APs may enable a better understanding and targeting of specific diseases.

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Full-length IL-33 regulates Smad3 phosphorylation and gene transcription in a distinctive AP2-dependent manner

Cited by 9 publications

References 47 publications

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

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

Ischemia reperfusion injury facilitates lung allograft acceptance through IL-33-mediated activation of donor-derived IL-5 producing group 2 innate lymphoid cells

Role of adaptin protein complexes in intracellular trafficking and their impact on diseases

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