scholarly journals Distinct signals and immune cells drive liver pathology and glomerulonephritis in ABIN1[D485N] mice

2019 ◽  
Vol 2 (6) ◽  
pp. e201900533 ◽  
Author(s):  
Sambit Kumar Nanda ◽  
Tsvetana Petrova ◽  
Francesco Marchesi ◽  
Marek Gierlinski ◽  
Momchil Razsolkov ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Liver Pathology ◽  
Disease Phenotype ◽  
Adaptive Immune ◽  
Inflammatory Monocytes ◽  
Diagnostic Potential ◽  
Ubiquitin Binding ◽  
Orally Active ◽  
Patrolling Monocytes

We report that TLR7, IL-6, and the adaptive immune system are essential for autoimmunity and glomerulonephritis but not for liver pathology in mice expressing the ubiquitin-binding–defective ABIN1[D485N] mutant. The blood and organs of ABIN1[D485N] mice have exceptionally high numbers of patrolling monocytes (pMo), which develop independently of IL-6 and the adaptive immune system. They are detectable in the blood months before autoimmunity and organ pathology are seen and may have diagnostic potential. The splenic pMo, inflammatory monocytes (iMo), and neutrophils of ABIN1[D485N] mice expressed high levels of mRNAs encoding proteins released during NETosis, which together with the high numbers of monocyte-derived dendritic cells (MoDCs) may drive the liver pathology in ABIN1[D485N] mice, and contribute to the pathology of other organs. The splenic iMo of ABIN1[D485N] mice displayed high expression of mRNAs encoding proteins controlling cell division and were actively dividing; this may underlie the increased pMo and MoDC numbers, which are derived from iMo. An orally active IRAK4 inhibitor suppressed all facets of the disease phenotype and prevented the increase in pMo numbers.

Evolution and age characteristics of the innate and adaptive immune system

2016 ◽  
Vol 75 (3) ◽  
pp. 74-84 ◽  
Author(s):  
A.E. Abaturov ◽  
◽  
E.A. Agafonova ◽  
N.I. Abaturova ◽  
V.L. Babich ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Adaptive Immune

scholarly journals Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System

2021 ◽  
Vol 8 (8) ◽  
pp. 2004979
Author(s):  
Jun‐Young Park ◽  
Sung Jean Park ◽  
Jun Young Park ◽  
Sang‐Hyun Kim ◽  
Song Kwon ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Protein Corona ◽  
Unfolded Protein ◽  
Adaptive Immune

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals Programming Native CRISPR Arrays for the Generation of Targeted Immunity

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Alexander P. Hynes ◽  
Simon J. Labrie ◽  
Sylvain Moineau
Keyword(s):  
Immune System ◽  
Nucleic Acid ◽  
Genome Editing ◽  
Dna Sequence ◽  
Adaptive Immune System ◽  
Natural Process ◽  
The Public ◽  
Adaptive Immune ◽  
Public Consciousness ◽  
Industrial Settings

ABSTRACT The adaptive immune system of prokaryotes, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes), results in specific cleavage of invading nucleic acid sequences recognized by the cell’s “memory” of past encounters. Here, we exploited the properties of native CRISPR-Cas systems to program the natural “memorization” process, efficiently generating immunity not only to a bacteriophage or plasmid but to any specifically chosen DNA sequence. IMPORTANCE CRISPR-Cas systems have entered the public consciousness as genome editing tools due to their readily programmable nature. In industrial settings, natural CRISPR-Cas immunity is already exploited to generate strains resistant to potentially disruptive viruses. However, the natural process by which bacteria acquire new target specificities (adaptation) is difficult to study and manipulate. The target against which immunity is conferred is selected stochastically. By biasing the immunization process, we offer a means to generate customized immunity, as well as provide a new tool to study adaptation.

scholarly journals Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo

2012 ◽  
Vol 10 (1) ◽  
pp. 201 ◽  
Author(s):  
Gezina TML Oei ◽  
Kirsten F Smit ◽  
Djai vd Vondervoort ◽  
Daniel Brevoord ◽  
Arjan Hoogendijk ◽  
...  
Keyword(s):  
Immune System ◽  
Healthy Volunteers ◽  
Ex Vivo ◽  
Adaptive Immune System ◽  
Adaptive Immune
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