Nicotine causes alternative polarization of macrophages via Src‐mediated STAT3 activation: Potential pathobiological implications

Abstract Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

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A homodimeric aptamer variant generated from ligand-guided selection activates T-cell receptor cluster of differentiation three complex

10.1101/2020.05.18.102145 ◽

2020 ◽

Author(s):

Lina Freage ◽

Deana Jamal ◽

Nicole Williams ◽

Prabodhika R. Mallikaratchy

Keyword(s):

T Cell ◽

Nucleic Acid ◽

T Cell Receptor ◽

T Cell Activation ◽

Cell Activation ◽

Cell Receptor ◽

Receptor Cluster ◽

Pharmacokinetic Properties ◽

Activation Potential ◽

Cluster Of Differentiation

AbstractRecently, immunotherapeutic modalities with engineered cells and monoclonal antibodies have been effective in treating several malignancies. However, growing evidence suggests that immune-related adverse events (irAE) lead to severe and long-term side effects. Most iRAEs involve prolonged circulation of antibodies. To address this problem, nucleic acid aptamers can serve as alternative molecules to design immunotherapeutics with high functional diversity and predictable circulation times. Here, we report the first synthetic prototype consisting of DNA aptamers, which can activate T-cell receptor cluster of differentiation 3 (TCR-CD3) complex in cultured T-cells. We show that activation potential is similar to that of a monoclonal antibody (mAb) against TCR-CD3, suggesting the potential of aptamers in developing efficacious synthetic immunomodulators. The synthetic prototype of anti-TCR-CD3ε, as described herein, was designed using aptamer ZUCH-1 against TCR-CD3ε, generated by Ligand Guided Selection (LIGS). Aptamer ZUCH-1 was truncated and modified with nuclease-resistant RNA analogs to enhance stability. Several dimeric analogs with truncated and modified variants were designed with variable linker lengths to investigate the activation potential of each construct. Among them, dimeric aptamer with approximate dimensions similar to those of an antibody showed the highest T-cell-activation, suggesting the importance of optimizing linker lengths in engineering functional aptamers. The observed activation potential of dimeric aptamers shows the vast potential of aptamers in designing synthetically versatile immunomodulators with tunable pharmacokinetic properties, expanding immunotherapeutic designs with the use of nucleic acid-based ligands such as aptamers.

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BRC1expression regulates bud activation potential but is not necessary or sufficient for bud growth inhibition inArabidopsis

Development ◽

10.1242/dev.145649 ◽

2017 ◽

Vol 144 (9) ◽

pp. 1661-1673 ◽

Cited By ~ 59

Author(s):

Madeleine Seale ◽

Tom Bennett ◽

Ottoline Leyser

Keyword(s):

Growth Inhibition ◽

Activation Potential ◽

Bud Growth

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Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?

Pathophysiology ◽

10.1016/j.pathophys.2018.08.002 ◽

2018 ◽

Vol 25 (4) ◽

pp. 397-404 ◽

Cited By ~ 3

Author(s):

Nahuel A. Ramella ◽

Isabel Andújar ◽

José L. Ríos ◽

Silvana A. Rosú ◽

M. Alejandra Tricerri ◽

...

Keyword(s):

Inflammatory Responses ◽

Human Apolipoprotein ◽

Apolipoprotein A ◽

Activation Potential ◽

Stimulation Of

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