scholarly journals Platelets Fuel the Inflammasome Activation of Innate Immune Cells

Cell Reports ◽  
2020 ◽  
Vol 31 (6) ◽  
pp. 107615 ◽  
Author(s):  
Verena Rolfes ◽  
Lucas Secchim Ribeiro ◽  
Ibrahim Hawwari ◽  
Lisa Böttcher ◽  
Nathalia Rosero ◽  
...  
Keyword(s):  
Immune Cells ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Cells

Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated?

2020 ◽  
Author(s):  
Rodolfo Perez-Alamino ◽  
Raquel Cuchacovich ◽  
Luis R. Espinoza ◽  
Constance P. Porretta ◽  
Arnold H. Zea
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Cells ◽  
Systemic Lupus

Uric acid-mediated inflammasome activation in IL-6 primed innate immune cells is regulated by baricitinib

2020 ◽  
Vol 31 (1) ◽  
pp. 270-275 ◽  
Author(s):  
Jumpei Temmoku ◽  
Yuya Fujita ◽  
Naoki Matsuoka ◽  
Takeshi Urano ◽  
Makiko Yashiro Furuya ◽  
...  
Keyword(s):  
Uric Acid ◽  
Immune Cells ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Cells

Role of Inflammasome Activation in Systemic Lupus Erythematosus: Are Innate Immune Cells Activated?

2021 ◽  
Vol 17 (4) ◽  
pp. 187-191
Author(s):  
Rodolfo Perez-Alamino ◽  
Raquel Cuchacovich ◽  
Luis R. Espinoza ◽  
Constance P. Porretta ◽  
Arnold H. Zea
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Cells ◽  
Systemic Lupus

scholarly journals Autophagy in Pulmonary Innate Immunity

2019 ◽  
Vol 12 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Lang Rao ◽  
N. Tony Eissa
Keyword(s):  
Reactive Oxygen Species ◽  
Innate Immunity ◽  
Cell Growth ◽  
Immune Cells ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Cells ◽  
Oxygen Species ◽  
Intracellular Digestion ◽  
Molecular Patterns

Autophagy is a major intracellular digestion system that delivers cytoplasmic components for degradation and recycling. In this capacity, autophagy plays an important role in maintaining cellular homeostasis by mediating the degradation of cellular macromolecules and dysfunctional organelles and regeneration of nutrients for cell growth. Autophagy is important in innate immunity, as it is responsible for the clearance of various pathogens. Deficiency of intracellular autophagy can result in exaggerated activation of the inflammasome. The latter is an innate immune complex that senses diverse pathogen-associated or danger-associated molecular patterns and activates the expression of inflammatory cytokines. In autophagy-deficient cells, accumulation of damaged organelles, misfolded proteins, and reactive oxygen species contribute to inflammasome activation. The lung is continuously exposed to pathogens from the environment, rendering it vulnerable to infection. The lung innate immune cells act as a crucial initial barrier against the continuous threat from pathogens. In this review, we will summarize recent findings on the regulation of autophagy and its inter­action with innate immunity, focusing on the lung.

scholarly journals Platelets Fuel the Inflammasome Activation of Innate Immune Cells

2019 ◽  
Author(s):  
Verena Rolfes ◽  
Lucas S. Ribeiro ◽  
Ibrahim Hawwari ◽  
Lisa Böttcher ◽  
Nathalia Rosero ◽  
...  
Keyword(s):  
Immune Cells ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Innate Immune Cells

scholarly journals IRAK1-mediated coincidence detection of microbial signals licenses inflammasome activation

2019 ◽  
Author(s):  
Sharat J. Vayttaden ◽  
Margery Smelkinson ◽  
Orna Ernst ◽  
Rebecca J. Carlson ◽  
Jing Sun ◽  
...  
Keyword(s):  
Immune Cells ◽  
Threat Assessment ◽  
Innate Immune ◽  
Coincidence Detection ◽  
Inflammasome Activation ◽  
Innate Immune Cells ◽  
Single Receptor ◽  
Innate Immune Signaling ◽  
Multiple Receptors ◽  
Increased Susceptibility

SummaryThe innate immune system signals through various higher order signaling complexes called supramolecular organizing centers (SMOCs), which typically organize components of a single pathway. While innate immune signaling pathways have been largely characterized using single receptor stimuli, responses to pathogens require the coordinated engagement of multiple pathways. Here, we report an IRAK1-containing SMOC formed specifically when multiple receptors are activated, which recruits select components of the TLR, MAPK and inflammasome pathways. This allows for signal flux redistribution from TLRs to inflammasomes and facilitates inflammasome licensing through an MKK7-JNK axis, which is defective in Irak1−/− mice. Furthermore, this defect in Irak1−/− mice manifests in increased susceptibility to inflammasome-sensitive pathogens and diminished IL1 production from inflammasomes after co-TLR priming. Thus, IRAK1 SMOCs form a multi-pathway coordinating hub for coincidence detection of microbial signals, which may be employed by innate immune cells as a threat assessment and thresholding mechanism for inflammasome activation.

scholarly journals Germline TIM-3 Mutations Characterize Sub-Cutaneous Panniculitis T-Cell Lymphomas with Hemophagocytic Lymphohistiocytic Syndrome

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1569-1569
Author(s):  
Dong-Anh Khuong-Quang ◽  
Tenzin Gayden ◽  
Fernando Sepulveda ◽  
Jonathan Pratt ◽  
Elvis Valera ◽  
...  
Keyword(s):  
T Cell ◽  
Board Of Directors ◽  
Immune Cells ◽  
Innate Immune ◽  
Hek293 Cells ◽  
Inflammasome Activation ◽  
Innate Immune Cells ◽  
Advisory Committees ◽  
T Cell Lymphomas ◽  
Life Threatening

Abstract Introduction Sub-cutaneous panniculitis T-cell lymphomas (SPTCL), a rare non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening activation of the immune system which adversely impacts survival. T-cell immunoglobulin mucin 3 (TIM-3) is a modulator of immune responses expressed on subgroups of T- and innate immune cells. In this work we describe the first germline variants associated with SPTCL, which are in the TIM-3 gene. Methods We sequenced 27 SPTCL cases to identify gene variants. We performed TIM-3 functional analysis on immune cells from patients and HEK293 cells engineered to overexpress wild-type or mutant TIM-3. Results We identified homozygous, germline, loss-of-function, missense variants in highly conserved residues of TIM-3, namely p.Y82C and p.I97M in about 60% (16/27) of SPTCL cases. These samples were drawn from cases series across 3 continents. Patients with bi-allelic TIM-3 mutations were younger at diagnosis, and several had life-threatening HLH and severe disease course. TIM-3 mutations show specific geographic distribution. Y82C TIM-3 mutations occur on a founder chromosome in patients with East-Asian and Polynesian ancestry, while I97M TIM-3 is observed in Caucasians. Both variants induce protein misfolding and cytoplasmic retention of TIM-3. Loss of TIM-3 membrane expression in TIM-3 mutants abrogates the PD-1/PDL-1 checkpoint and prevents the termination of a Th1-immune response. In HEK293 cells, mutant TIM-3 was not expressed on the cell surface. Defective TIM-3 expression leads to persistent immune activation with increased production of inflammatory cytokines including TNF-alpha and IL-1beta by innate immune cells. Conclusion Our findings highlight HLH/SPTCL as a new genetic entity where loss of the TIM-3 immune checkpoint is associated with T-cell infiltration of adipose tissue and inflammasome activation. This is the first causative germline defect identified in SPTCL. While our findings indicate that TIM-3-mutant HLH/SPTCL benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint could have serious adverse consequences. Disclosures Prince: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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