Abstract
Motivated by several recent experimental observations that vitamin-D could interact with antigen presenting cells (APCs) and T-lymphocyte cells (T-cells) to promote and to regulate different stages of immune response, we developed a coarse grained but general kinetic model in an attempt to capture the role of vitamin-D in immunomodulatory responses. Our kinetic model, developed using the ideas of chemical network theory, leads to a system of nine coupled equations that we solve both by direct and by stochastic (Gillespie) methods. Both the analyses consistently provide detail information on the dependence of immune response to the variation of critical rate parameters. We find that although vitamin-D plays a negligible role in the initial immune response, it exerts a profound influence in the long term, especially in helping the system to achieve a new, stable steady state. The study explores the role of vitamin-D in preserving an observed bistability in the phase diagram (spanned by system parameters) of immune regulation, thus allowing the response to tolerate a wide range of pathogenic stimulation which could help in resisting autoimmune diseases. We also study how vitamin-D affects the time dependent population of dendritic cells that connect between innate and adaptive immune responses. Variations in dose dependent response of anti-inflammatory and pro-inflammatory T-cell populations to vitamin-D correlate well with recent experimental results. Our kinetic model allows for an estimation of the range of optimum level of vitamin-D required for smooth functioning of the immune system and for control of both hyper-regulation and inflammation. Most importantly, the present study reveals that an overdose or toxic level of vitamin-D or any steroid analogue could give rise to too large a tolerant response, leading to an inefficacy in adaptive immune function.
Highlights
Vitamin-D is reported to be involved in large number of distinct immune responses [1,2,3,4,5,6], our quantitative understanding of these processes at the cellular level still remains largely incomplete
The important constituents of the model considered here are the following: (i) pathogen (It is important to note that, in our analyses we have considered pathogen, as a numerical quantity ‘‘P’’ that is capable of eliciting T-lymphocyte cells (T-cells) mediated immune response), (ii) naive T-cell, (iii) myeloid dendritic cell in the form of professional antigen presenting cells (APC), both in their resting and activated forms (iv) effector and regulatory T-cells, (v) inactive vitamin-D (25(OH)D3) and active vitamin-D (1,25(OH)2D3)
A healthy immune system usually functions with a balanced regulation that controls the population of effector T-cells to an appropriate level which is adequate for the clearance of pathogens
Summary
Vitamin-D is reported to be involved in large number of distinct immune responses [1,2,3,4,5,6], our quantitative understanding of these processes at the cellular level still remains largely incomplete. This is because of the enormous complexity of human immune system which depends on a large number of interacting (some may be still unknown) components. Beyond its established classical function in calcium metabolism, studies on vitamin-D are progressively focused on its pleiotropic actions [1,2,3,4,5,6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
