scholarly journals Phosphoinositide 3-kinase δ (PI3Kδ) in respiratory disease

2018 ◽  
Vol 46 (2) ◽  
pp. 361-369 ◽  
Author(s):  
Clare A. Stokes ◽  
Alison M. Condliffe
Keyword(s):  
Airway Inflammation ◽  
Cell Function ◽  
Immune Cell ◽  
Respiratory Infections ◽  
Therapeutic Option ◽  
Neutrophil Function ◽  
Histone Deacetylase 2 ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Adaptive Immune Cell

Defining features of chronic airway diseases include abnormal and persistent inflammatory processes, impaired airway epithelial integrity and function, and increased susceptibility to recurrent respiratory infections. Phosphoinositide 3-kinases (PI3K) are lipid kinases, which contribute to multiple physiological and pathological processes within the airway, with abnormal PI3K signalling contributing to the pathogenesis of several respiratory diseases. Consequently, the potential benefit of targeting PI3K isoforms has received considerable attention, being viewed as a viable therapeutic option in inflammatory and infectious lung disorders. The class I PI3K isoform, PI3Kδ (Phosphoinositide 3-kinases δ) is of particular interest given its multiple roles in modulating innate and adaptive immune cell functions, airway inflammation and corticosteroid sensitivity. In this mini-review, we explore the role of PI3Kδ in airway inflammation and infection, focusing on oxidative stress, ER stress, histone deacetylase 2 and neutrophil function. We also describe the importance of PI3Kδ in adaptive immune cell function, as highlighted by the recently described Activated PI3K Delta Syndrome, and draw attention to some of the potential clinical applications and benefits of targeting this molecule.

1675-P: Adipocyte Adaptive Immune Cell Function and Exhaustion Contribute to the Drop in Adipose Tissue (AT) Regulatory T-Cells (Tregs) in Human Obesity

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1675-P
Author(s):  
DAVID BRADLEY ◽  
ALECIA M. BLASZCZAK ◽  
ALAN SMITH ◽  
ANAHITA D. JALILVAND ◽  
VALERIE P. WRIGHT ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Human Obesity ◽  
Adaptive Immune ◽  
Adaptive Immune Cell

scholarly journals The Alzheimer’s disease-associated protective Plcγ2-P522R variant promotes immune functions

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Mari Takalo ◽  
Rebekka Wittrahm ◽  
Benedikt Wefers ◽  
Samira Parhizkar ◽  
Kimmo Jokivarsi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Cell ◽  
Therapeutic Option ◽  
Immune Functions ◽  
Disease Etiology ◽  
Cell Functions ◽  
Bv2 Microglia ◽  
Brain Mrna ◽  
Protective Variant

Abstract Background Microglia-specific genetic variants are enriched in several neurodegenerative diseases, including Alzheimer’s disease (AD), implicating a central role for alterations of the innate immune system in the disease etiology. A rare coding variant in the PLCG2 gene (rs72824905, p.P522R) expressed in myeloid lineage cells was recently identified and shown to reduce the risk for AD. Methods To assess the role of the protective variant in the context of immune cell functions, we generated a Plcγ2-P522R knock-in (KI) mouse model using CRISPR/Cas9 gene editing. Results Functional analyses of macrophages derived from homozygous KI mice and wild type (WT) littermates revealed that the P522R variant potentiates the primary function of Plcγ2 as a Pip2-metabolizing enzyme. This was associated with improved survival and increased acute inflammatory response of the KI macrophages. Enhanced phagocytosis was observed in mouse BV2 microglia-like cells overexpressing human PLCγ2-P522R, but not in PLCγ2-WT expressing cells. Immunohistochemical analyses did not reveal changes in the number or morphology of microglia in the cortex of Plcγ2-P522R KI mice. However, the brain mRNA signature together with microglia-related PET imaging suggested enhanced microglial functions in Plcγ2-P522R KI mice. Conclusion The AD-associated protective Plcγ2-P522R variant promotes protective functions associated with TREM2 signaling. Our findings provide further support for the idea that pharmacological modulation of microglia via TREM2-PLCγ2 pathway-dependent stimulation may be a novel therapeutic option for the treatment of AD.

scholarly journals Glucose Triggers ATP Secretion from Bacteria in a Growth-Phase-Dependent Manner

2013 ◽  
Vol 79 (7) ◽  
pp. 2328-2335 ◽  
Author(s):  
Ippei Hironaka ◽  
Tadayuki Iwase ◽  
Shinya Sugimoto ◽  
Ken-ichi Okuda ◽  
Akiko Tajima ◽  
...  
Keyword(s):  
Stationary Phase ◽  
Growth Phase ◽  
Cell Function ◽  
Immune Cell ◽  
Dependent Manner ◽  
T Helper 17 ◽  
Content Type ◽  
Cell Functions ◽  
Atp Secretion ◽  
Enterococcus Gallinarum

ABSTRACTATP modulates immune cell functions, and ATP derived from gut commensal bacteria promotes the differentiation of T helper 17 (Th17) cells in the intestinal lamina propria. We recently reported thatEnterococcus gallinarum, isolated from mice and humans, secretes ATP. We have since found and characterized several ATP-secreting bacteria. Of the tested enterococci,Enterococcus mundtiisecreted the greatest amount of ATP (>2 μM/108cells) after overnight culture. Glucose, not amino acids and vitamins, was essential for ATP secretion fromE. mundtii. Analyses of energy-deprived cells demonstrated that glycolysis is the most important pathway for bacterial ATP secretion. Furthermore, exponential-phaseE. mundtiiandEnterococcus faecaliscells secrete ATP more efficiently than stationary-phase cells. Other bacteria, includingPseudomonas aeruginosa,Escherichia coli, andStaphylococcus aureus, also secrete ATP in exponential but not stationary phase. These results suggest that various gut bacteria, including commensals and pathogens, might secrete ATP at any growth phase and modulate immune cell function.

scholarly journals Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation

2018 ◽  
Vol 9 ◽  
Author(s):  
Jennifer Brasseit ◽  
Cheong K. C. Kwong Chung ◽  
Mario Noti ◽  
Daniel Zysset ◽  
Nina Hoheisel-Dickgreber ◽  
...  
Keyword(s):  
Immune Cell ◽  
Intestinal Inflammation ◽  
Interferon Γ ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Adaptive Immune ◽  
Adaptive Immune Cell
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