scholarly journals Bifurcations and Multistability in a Model of Cytokine-Mediated Autoimmunity

2019 ◽  
Vol 29 (03) ◽  
pp. 1950034 ◽  
Author(s):  
Farzad Fatehi ◽  
Yuliya N. Kyrychko ◽  
Robert Molchanov ◽  
Konstantin B. Blyuss
Keyword(s):  
T Cells ◽  
Chronic Infection ◽  
Initial Conditions ◽  
Cell Activity ◽  
Basins Of Attraction ◽  
Activity Analysis ◽  
Steady States ◽  
System Parameters ◽  
Stability And Bifurcations

This paper investigates the dynamics of immune response and autoimmunity with particular emphasis on the role of regulatory T cells (Tregs), T cells with different activation thresholds, and cytokines in mediating T cell activity. Analysis of the steady states yields parameter regions corresponding to regimes of normal clearance of viral infection, chronic infection, or autoimmune behavior, and the boundaries of stability and bifurcations of relevant steady states are found in terms of system parameters. Numerical simulations are performed to illustrate different dynamical scenarios, and to identify basins of attraction of different steady states and periodic solutions, highlighting the important role played by the initial conditions in determining the outcome of immune interactions.

scholarly journals The abscopal effect of radiation therapy

2021 ◽  
Vol 17 (13) ◽  
pp. 1683-1694
Author(s):  
Daniel J Craig ◽  
Nisha S Nanavaty ◽  
Monika Devanaboyina ◽  
Laura Stanbery ◽  
Danae Hamouda ◽  
...  
Keyword(s):  
T Cells ◽  
Radiation Therapy ◽  
Cytotoxic T Cells ◽  
Cell Activity ◽  
The Body ◽  
Abscopal Effect ◽  
Sting Pathway ◽  
And Migration ◽  
Anticancer Response

Radiation therapy (RT) in some cases results in a systemic anticancer response known as the abscopal effect. Multiple hypotheses support the role of immune activation initiated by RT-induced DNA damage. Optimal radiation dose is necessary to promote the cGAS-STING pathway in response to radiation and initiate an IFN-1 signaling cascade that promotes the maturation and migration of dendritic cells to facilitate antigen presentation and stimulation of cytotoxic T cells. T cells then exert a targeted response throughout the body at areas not subjected to RT. These effects are further augmented through the use of immunotherapeutic drugs resulting in increased T-cell activity. Tumor-infiltrating lymphocyte presence and TREX1, KPNA2 and p53 signal expression are being explored as prognostic biomarkers.

scholarly journals Role of Phosphodiesterase 7 (PDE7) in T Cell Activity. Effects of Selective PDE7 Inhibitors and Dual PDE4/7 Inhibitors on T Cell Functions

2020 ◽  
Vol 21 (17) ◽  
pp. 6118 ◽  
Author(s):  
Marianna Szczypka
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Splice Variants ◽  
Cell Activity ◽  
Cell Functions ◽  
Simultaneous Inhibition ◽  
And Function

Phosphodiesterase 7 (PDE7), a cAMP-specific PDE family, insensitive to rolipram, is present in many immune cells, including T lymphocytes. Two genes of PDE7 have been identified: PDE7A and PDE7B with three or four splice variants, respectively. Both PDE7A and PDE7B are expressed in T cells, and the predominant splice variant in these cells is PDE7A1. PDE7 is one of several PDE families that terminates biological functions of cAMP—a major regulating intracellular factor. However, the precise role of PDE7 in T cell activation and function is still ambiguous. Some authors reported its crucial role in T cell activation, while according to other studies PDE7 activity was not pivotal to T cells. Several studies showed that inhibition of PDE7 by its selective or dual PDE4/7 inhibitors suppresses T cell activity, and consequently T-mediated immune response. Taken together, it seems quite likely that simultaneous inhibition of PDE4 and PDE7 by dual PDE4/7 inhibitors or a combination of selective PDE4 and PDE7 remains the most interesting therapeutic target for the treatment of some immune-related disorders, such as autoimmune diseases, or selected respiratory diseases. An interesting direction of future studies could also be using a combination of selective PDE7 and PDE3 inhibitors.

scholarly journals Dynamics and Patterns of a Diffusive Prey-Predator System with a Group Defense for Prey

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Honglan Zhu ◽  
Xuebing Zhang
Keyword(s):  
Neumann Boundary Condition ◽  
Critical Role ◽  
Neumann Boundary ◽  
Steady States ◽  
Spatiotemporal Patterns ◽  
System Parameters ◽  
Existence And Nonexistence ◽  
Group Defense ◽  
Predator System

We study a diffusive prey-predator system with a group defense for prey. Under Neumann boundary condition, we analyze local and stability of nonnegative constant steady states and the existence and nonexistence of nonconstant steady states. These results also exhibit the critical role of the system parameters leading to the formation of spatiotemporal patterns.

SYNCHRONIZATION OF SLOWLY ROTATING PENDULUMS

2012 ◽  
Vol 22 (05) ◽  
pp. 1250128 ◽  
Author(s):  
K. CZOLCZYNSKI ◽  
P. PERLIKOWSKI ◽  
A. STEFANSKI ◽  
T. KAPITANIAK
Keyword(s):  
Initial Conditions ◽  
Basins Of Attraction ◽  
System Parameters ◽  
Initial Transient ◽  
Horizontal Beam ◽  
Parallel Surface ◽  
Wide Range ◽  
Phase Differences

We study synchronization of a number of rotating pendulums mounted on a horizontal beam which can roll on the parallel surface. It has been shown that after the initial transient, different states of pendulums synchronization occur. We derive the analytical equations for the estimation of the phase differences between phase synchronized pendulums. After the study of the basins of attraction of different synchronization states, we argue that the observed phenomena are robust as they occur for a wide range of both initial conditions and system parameters.

scholarly journals Brucella abortus and Pregnancy in Mice: Impact of Chronic Infection on Fertility and the Role of Regulatory T Cells in Tissue Colonization

2020 ◽  
Vol 88 (10) ◽  
Author(s):  
Shakirat A. Adetunji ◽  
Denise L. Faustman ◽  
L. Garry Adams ◽  
Daniel G. Garcia-Gonzalez ◽  
Martha E. Hensel ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Brucella Abortus ◽  
Chronic Infection ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Critical Role ◽  
Fine Tuning ◽  
Content Type

ABSTRACT Stealthy intracellular bacterial pathogens are known to establish persistent and sometimes lifelong infections. Some of these pathogens also have a tropism for the reproductive system, thereby increasing the risk of reproductive disease and infertility. To date, the pathogenic mechanism involved remains poorly understood. Here, we demonstrate that Brucella abortus, a notorious reproductive pathogen, has the ability to infect the nonpregnant uterus, sustain infection, and induce inflammatory changes during both acute and chronic stages of infection. In addition, we demonstrated that chronically infected mice had a significantly reduced number of pregnancies compared to naive controls. To investigate the immunologic mechanism responsible for uterine tropism, we explored the role of regulatory T cells (Tregs) in the pathogenesis of Brucella abortus infection. We show that highly suppressive CD4+FOXP3+TNFR2+ Tregs contribute to the persistence of Brucella abortus infection and that inactivation of Tregs with tumor necrosis factor receptor II (TNFR2) antagonistic antibody protected mice by significantly reducing bacterial burden both systemically and within reproductive tissues. These findings support a critical role of Tregs in the pathogenesis of persistence induced by intracellular bacterial pathogens, including B. abortus. Results from this study indicate that adverse reproductive outcomes can occur as sequelae of chronic infection in nonpregnant animals and that fine-tuning Treg activity may provide novel immunotherapeutic and prevention strategies against intracellular bacterial infections such as brucellosis.

scholarly journals THE LONG RUN OUTCOMES AND GLOBAL DYNAMICS OF A DUOPOLY GAME WITH MISSPECIFIED DEMAND FUNCTIONS

2004 ◽  
Vol 06 (03) ◽  
pp. 343-379 ◽  
Author(s):  
GIAN-ITALO BISCHI ◽  
CARL CHIARELLA ◽  
MICHAEL KOPEL
Keyword(s):  
Demand Function ◽  
Initial Conditions ◽  
Basins Of Attraction ◽  
Steady States ◽  
Model Parameters ◽  
Global Dynamics ◽  
Market Demand ◽  
Economic Significance ◽  
Reaction Functions ◽  
Long Run

In this paper we study a model of a quantity-setting duopoly market where firms lack knowledge of the market demand. Using a misspecified demand function firms determine their profit-maximizing choices of their corresponding perceived market game. For illustrative purposes we assume that the (true) demand function is linear and that the reaction functions of the players are quadratic. We then investigate the global dynamics of this game and characterize the number of steady states and their welfare properties. We study the basins of attraction of these steady states and present situations in which global bifurcations of their basins occur when model parameters are varied. The economic significance of our result is to show that in situations where players choose their actions based on a misspecified model of the environment, additional self-confirming steady states may emerge, despite the fact that the Nash-equilibrium of the game under perfect knowledge is unique. As a consequence the long run outcome of the game and overall welfare is highly dependent upon initial conditions.

Regulation of B Cell Activity in Man: Role of T Cells

1979 ◽  
Vol 45 (1) ◽  
pp. 3-39 ◽  
Author(s):  
Rudy E. Ballieux ◽  
Cobi J. Heijnen ◽  
Fons Uytdehaag ◽  
Ben J. M. Zegers
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cell Activity

scholarly journals CLEC4s as Potential Therapeutic Targets in Hepatocellular Carcinoma Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Yinjiang Zhang ◽  
Hongyun Wei ◽  
Lu Fan ◽  
Mingyan Fang ◽  
Xu He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Potential Role ◽  
Immune Cell ◽  
Mrna Level ◽  
Cell Activity ◽  
Expression Level ◽  
Cell Trafficking

Immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) is critical in tumor development. C-type (Ca2+ -dependent) lectin (CLEC) receptors, essential in innate pattern recognition, have potential regulatory effects on immune cell trafficking and modulatory effects on cancer cell activity. However, information on the expression and prognostic value of CLECs in HCC is scanty. Herein, we explored the potential role of CLECs in HCC based on TCGA, ONCOMINE, GEPIA, UALCAN, cBioPortal, Metascape, TRRUST, and TIMER databases. Results demonstrated a significantly higher mRNA level of CLEC4A and CLEC4L in HCC tissues than normal liver tissues. Contrarily, we found significantly low CLEC4G/H1/H2/M expression in HCC tissues. The IHC analysis revealed the following: Absence of CLEC4A/J/K/M in normal and liver cancer tissues; high CLEC4C expression in HCC tissues; low expression and zero detection of CLEC4D/E/H1/H2/L in HCC tissues and normal tissues, respectively. And the HepG2 and LX-2 were used to verify the expression level of CLEC4s via qRT-PCR in vitro. Furthermore, the expression of CLEC4H1 (ASGR1) and CLEC4H2 (ASGR2) exhibited a significant relation to clinical stages. However, the expression of CLEC4A, CLEC4D, CLEC4E, CLEC4J (FCER2), CLEC4K (CD207), CLEC4G, CLEC4H1, CLEC4M, and CLEC4H2 decreased with tumor progression. Patients expressing higher CLEC4H1/H2 levels had longer overall survival than patients exhibiting lower expression. Moreover, CLEC4A/D/E/J/K/G/H1/M/H2 had significant down-regulated levels of promoter methylation. The expression level of CLEC4s was correlated with the infiltration of B cells, CD8 + T cells, CD4 + T cells, macrophage cells, neutrophil cells, and dendritic cells. Functional analysis revealed the potential role of CLECL4s in virus infection, including COVID-19. Also, hsa-miR-4278 and hsa-miR-324-5p, two potential miRNA targets of CLEC4s, were uncovered. This article demonstrates that CLEC4 is crucial for the development of HCC and is associated with infiltration of various immune cells, providing evidence for new immunotherapy targets in HCC.

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