L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis

Joshi, Hemant; Almgren-Bell, Alison; Anaya, Edgar; Todd, Elizabeth M.; Dyken, Steven J. Van; Seth, Anushree; McIntire, Katherine M.; Singamaneni, Srikanth; Sutterwala, Fayyaz S.; Morley, Sharon Celeste

doi:10.1016/j.celrep.2022.110507

Cited by 23 publications

(18 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several co-activators of NLRP3 have been identified, including dsDNA-binding protein PKR [ 130 ], guanylate-binding protein GBP5 [ 131 ], receptor for activated C kinase RACK1 [ 132 ], Bruton tyrosine kinase BTK [ 133 , 134 , 135 ], actin-bundling protein L-plastin [ 136 ], stress granule protein DDX3X [ 137 ], NLRP11 [ 138 ], and NIMA-related kinase NEK7 [ 139 , 140 , 141 ]. Among them, NEK7 is an essential component of the NLRP3 inflammasome, but not NLRC4 or AIM2 inflammasomes, and the assembly of NEK7 and NLRP3 requires the K + efflux [ 139 ].…”

Section: Cellular Mechanisms Driving Nlrp3 Inflammasome Activationmentioning

confidence: 99%

Activation and Pharmacological Regulation of Inflammasomes

Chen

2022

Biomolecules

View full text Add to dashboard Cite

Inflammasomes are intracellular signaling complexes of the innate immune system, which is part of the response to exogenous pathogens or physiological aberration. The multiprotein complexes mainly consist of sensor proteins, adaptors, and pro-caspase-1. The assembly of the inflammasome upon extracellular and intracellular cues drives the activation of caspase-1, which processes pro-inflammatory cytokines IL-1β and IL-18 to maturation and gasdermin-D for pore formation, leading to pyroptosis and cytokine release. Inflammasome signaling functions in numerous infectious or sterile inflammatory diseases, including inherited autoinflammatory diseases, metabolic disorders, cardiovascular diseases, cancers, neurodegenerative disorders, and COVID-19. In this review, we summarized current ideas on the organization and activation of inflammasomes, with details on the molecular mechanisms, regulations, and interventions. The recent developments of pharmacological strategies targeting inflammasomes as disease therapeutics were also covered.

show abstract

Section: Cellular Mechanisms Driving Nlrp3 Inflammasome Activationmentioning

confidence: 99%

Activation and Pharmacological Regulation of Inflammasomes

Chen

2022

Biomolecules

View full text Add to dashboard Cite

show abstract

“…IL-1β secretion depends upon a priming signal and inflammasome activation ( Gritsenko et al., 2020 ). We treated alveolar macrophages with LPS, followed by nigericin, which leads to cleavage of pro-IL-1β and secretion of IL-1β in the extracellular space ( Figure 4 A) ( Joshi et al., 2022 ). Using the FluoroDOT assay, we detected IL-1β secretion 30 min after NLRP3 activation by nigericin.…”

Section: Resultsmentioning

confidence: 99%

High-resolution imaging of protein secretion at the single-cell level using plasmon-enhanced FluoroDOT assay

Seth

Mittal

Luan

et al. 2022

Cell Reports Methods

Self Cite

View full text Add to dashboard Cite

“…LPL has been shown to regulate mechanotransduction in macrophages ( 65 ). WT macrophages incubated upon softer substrates produced more IL-1β in response to NLRP3 inflammasome activation.…”

Section: Discussionmentioning

confidence: 99%

“…WT macrophages incubated upon softer substrates produced more IL-1β in response to NLRP3 inflammasome activation. However, LPL-deficient macrophages produced the same, reduced amount of IL-1 β following NLRP3 activation, and were unresponsive to varying substrate stiffnesses ( 65 ). Mechanotransudction in LPL-deficient macrophages was disrupted due to the mislocalization of the kinase Pyk2.…”

Section: Discussionmentioning

confidence: 99%

Efficient T Cell Migration and Activation Require L-Plastin

Joshi

Morley

2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T cells. LPL- deficient T cells migrate slowly in response to chemo-attractants such as CXCL12, CCL19, and poorly polarize towards ICAM-1. Loss of LPL impairs thymic egress and intranodal motility. LPL is also required for T-cell IS maturation with APCs, and therefore for efficient cytokine production and proliferation. LPL-/- mice are less susceptible to T-cell mediated pathologies, such as allograft rejection and experimental autoimmune encephalomyelitis (EAE). LPL activity is regulated by its N-terminal “headpiece”, which contains serine and threonine phosphorylation and calcium- and calmodulin-binding sites. LPL phosphorylation is required for lamellipodia formation during adhesion and migration, and also for LFA-1 clustering during IS formation. However, the precise molecular interactions by which LPL supports T-cell functional responses remain unclear. Future studies elucidating LPL-mediated regulation of T-cell migration and/or activation may illuminate pathways for therapeutic targeting in T-cell-mediated diseases.

show abstract

L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis

Cited by 23 publications

References 86 publications

Activation and Pharmacological Regulation of Inflammasomes

Activation and Pharmacological Regulation of Inflammasomes

High-resolution imaging of protein secretion at the single-cell level using plasmon-enhanced FluoroDOT assay

Efficient T Cell Migration and Activation Require L-Plastin

Contact Info

Product

Resources

About