scholarly journals Identifying Molecular Mechanisms Controlling Immune Cell Function

2020 ◽  
Author(s):  
Elke Glasmacher
Keyword(s):  
Molecular Mechanisms ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function

scholarly journals A Functional Interplay between 5-Lipoxygenase andμ-Calpain Affects Survival and Cytokine Profile of Human Jurkat T Lymphocyte Exposed to Simulated Microgravity

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Valeria Gasperi ◽  
Cinzia Rapino ◽  
Natalia Battista ◽  
Monica Bari ◽  
Nicolina Mastrangelo ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Molecular Mechanisms ◽  
Simulated Microgravity ◽  
Cell Function ◽  
Immune Cell ◽  
Apoptotic Cell ◽  
Immune Cell Function ◽  
Space Flights ◽  
Apoptotic Death ◽  
Mammalian Tissues

A growing body of evidence strongly indicates that both simulated and authentic weightlessness exert a broad range of effects on mammalian tissues and cells, including impairment of immune cell function and increased apoptotic death. We previously reported that microgravity-dependent activation of 5-lipoxygenase (5-LOX) might play a central role in the initiation of apoptosis in human T lymphocytes, suggesting that the upregulation of this enzyme might be (at least in part) responsible for immunodepression observed in astronauts during space flights. Herein, we supplement novel information about the molecular mechanisms underlying microgravity-triggered apoptotic cell death and immune system deregulation, demonstrating that under simulated microgravity human Jurkat T cells increase the content of cytosolic DNA fragments and cytochrome c (typical hallmarks of apoptosis) and have an upregulated expression and activity ofµ-calpain. These events were paralleled by the unbalance of interleukin- (IL-) 2 and interferon- (INF-)γ, anti- and proapoptotic cytokines, respectively, that seemed to be dependent on the functional interplay between 5-LOX andµ-calpain. Indeed, we report unprecedented evidence that 5-LOX inhibition reduced apoptotic death, restored the initial IL-2/INF-γratio, and more importantly revertedµ-calpain activation induced by simulated microgravity.

scholarly journals A folding switch regulates interleukin 27 biogenesis and secretion of its α-subunit as a cytokine

2019 ◽  
Vol 116 (5) ◽  
pp. 1585-1590 ◽  
Author(s):  
Stephanie I. Müller ◽  
Antonie Friedl ◽  
Isabel Aschenbrenner ◽  
Julia Esser-von Bieren ◽  
Martin Zacharias ◽  
...  
Keyword(s):  
Protein Folding ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Immune Cell ◽  
Single Amino Acid ◽  
Interleukin 12 ◽  
Signaling Proteins ◽  
Immune Cell Function ◽  
Close Link ◽  
Α Subunit

A common design principle of heteromeric signaling proteins is the use of shared subunits. This allows encoding of complex messages while maintaining evolutionary flexibility. How cells regulate and control assembly of such composite signaling proteins remains an important open question. An example of particular complexity and biological relevance is the interleukin 12 (IL-12) family. Four functionally distinct αβ heterodimers are assembled from only five subunits to regulate immune cell function and development. In addition, some subunits act as independent signaling molecules. Here we unveil key molecular mechanisms governing IL-27 biogenesis, an IL-12 family member that limits infections and autoimmunity. In mice, the IL-27α subunit is secreted as a cytokine, whereas in humans only heterodimeric IL-27 is present. Surprisingly, we find that differences in a single amino acid determine if IL-27α can be secreted autonomously, acting as a signaling molecule, or if it depends on heterodimerization for secretion. By combining computer simulations with biochemical experiments, we dissect the underlying structural determinants: a protein folding switch coupled to disulfide bond formation regulates chaperone-mediated retention versus secretion. Using these insights, we rationally change folding and assembly control for this protein. This provides the basis for a more human-like IL-27 system in mice and establishes a secretion-competent human IL-27α that signals on its own and can regulate immune cell function. Taken together, our data reveal a close link between protein folding and immunoregulation. Insights into the underlying mechanisms can be used to engineer immune modulators.

scholarly journals OP0013 SEX DIFFERENCES IN AUTOIMMUNE DISEASE SUSCEPTIBILITY; A MULTI-OMIC APPROACH

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 8.1-8
Author(s):  
G. Robinson ◽  
K. Waddington ◽  
J. Peng ◽  
A. Radziszewska ◽  
H. Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
Lipid Metabolism ◽  
Sex Hormones ◽  
Cell Function ◽  
Immune Cell ◽  
Density Lipoprotein ◽  
Hormone Treatment ◽  
Immune Cell Function ◽  
Immune Cell Subsets ◽  
Males And Females

Background:Males and females have altered immune responses resulting in variation in autoimmune and cardiovascular disease risk (CVR). Recently, these differences have played a role in the inflammatory response to COVID-19. Sex differences exist in the frequency and activity of immune-cell subsets but mechanisms underlying sexual dimorphism remain unknown. Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder that commonly emerges during puberty, has a strong female prevalence (female:male ratio, 4.5:1) and results in an increased CVR. JSLE is characterised by chronic inflammation and dyslipidaemia, where cardiovascular disease is a leading cause of mortality for patients. Our previous work identified a link between immune cell function and lipid metabolism in adult-onset SLE. We hypothesised that sex hormones could influence both lipid metabolism and immune cell function and this could determine sex-specific susceptibility to JSLE and associated CVR.Objectives:We investigated the role of sex hormones in modifying systemic lipid metabolism and inflammation.Methods:Nuclear magnetic resonance spectroscopy based serum metabolomics measuring over 130 lipoproteins (14-subsets with lipid compositions), flow cytometry measuring immune-cells, and RNA-sequencing were used to assess the metabolic and immune profile in young, pre/post-pubertal males (n=10/17) and females (n=10/23) and in individuals with gender-dysphoria (GD) under cross-hormone treatment (trans-male/female, n=26/25). This analysis was also performed on a cohort of post-pubertal male (n=12) and female (n=23) JSLE patients. Data was analysed by logistic regression, balanced random forest machine learning (BRF-ML), differential gene expression (DEG) and pathway analysis.Results:Post-pubertal males had significantly reduced cardio-protective high-density lipoprotein (HDL) subsets (p<0.0001) and increased cardio-pathogenic very-low-density lipoprotein subsets (p<0.0001) compared to females. These differences were not observed pre-puberty and were reversed significantly by cross-hormone treatment in GD individuals, suggesting that sex hormones regulate lipid metabolism in-vivo.BRF-ML (28 immune-cell subsets) identified an increased frequency of anti-inflammatory regulatory T-cells (Tregs) in post-pubertal males compared to females (p=0.0097). These Tregs were also more suppressive in males compared to females. Differences in Treg frequency were seen pre-puberty and were not altered by sex hormone treatment in GD individuals. However, Treg DEGs and functional transcriptomic pathways altered between post-pubertal males and females, including those involved in inflammatory signalling, overlapped with those altered by hormones in GD, suggesting hormones may also drive Treg functional changes. In addition, HDL metabolites modified by hormones showed differential associations with Treg phenotypes between post-pubertal males and females.Strikingly, sex differences in lipoproteins and Tregs were lost in JSLE, suggesting hormone signalling could be dysregulated in the pathogenesis of autoimmunity and could increase CVR for patients.Conclusion:Sex hormones drive altered lipoprotein metabolism and functional transcriptomic pathways in Tregs. Males have a lipoprotein profile associated with increased CVR, but a more anti-inflammatory immune profile compared to females. Together, this could explain sex differences in inflammatory disease susceptibilities and inform future sex-specific therapeutic strategies for the management of both JSLE and CVR.Acknowledgements:Lupus UKRosetrees TrustVersus ArthritisNIHR UCLH Biomedical Research CentreDisclosure of Interests:None declared

scholarly journals Pre-Transplant Immune Cell Function Assay as a Predictor of Early Cardiac Allograft Rejection

2021 ◽  
Vol 40 (4) ◽  
pp. S232-S233
Author(s):  
S.D. Maidman ◽  
C. Gidea ◽  
A. Reyentovich ◽  
S. Rao ◽  
T. Saraon ◽  
...  
Keyword(s):  
Allograft Rejection ◽  
Cell Function ◽  
Immune Cell ◽  
Cardiac Allograft ◽  
Immune Cell Function ◽  
Cardiac Allograft Rejection

scholarly journals Cellular and metabolic mechanisms of nutrient actions in immune function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip Newsholme
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Vitamin D ◽  
Immune System ◽  
Cell Function ◽  
Immune Cell ◽  
Cell Structure ◽  
Nutritional Intervention ◽  
Immune Cell Function ◽  
And Function

AbstractVarious nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of diverse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.

Utility of an immune cell function assay to differentiate rejection from infectious enteritis in pediatric intestinal transplant recipients

2014 ◽  
Vol 28 (2) ◽  
pp. 229-235 ◽  
Author(s):  
Laura J. Wozniak ◽  
Robert S. Venick ◽  
Sherilyn Gordon Burroughs ◽  
Khiet D. Ngo ◽  
John P. Duffy ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Transplant Recipients ◽  
Intestinal Transplant

Supplementation with Selenium Restores Age-Related Decline in Immune Cell Function

1995 ◽  
Vol 209 (4) ◽  
pp. 369-375 ◽  
Author(s):  
M. Roy ◽  
L. Kiremidjian-Schumacher ◽  
H. I. Wishe ◽  
M. W. Cohen ◽  
G. Stotzky
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Immune Cell Function ◽  
Age Related

scholarly journals MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function

2015 ◽  
Vol 9 (4) ◽  
pp. 974-985 ◽  
Author(s):  
R Brauer ◽  
J Tureckova ◽  
I Kanchev ◽  
M Khoylou ◽  
J Skarda ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Immune Cell Function
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