title: A stochastic chemical dynamic approach to correlate autoimmunity and optimal vitamin-D range.
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.
authors: SSCU, Indian Institute of Science, Bangalore, Karnataka, India.
authors: Susmita
authors: S
authors: Roy
authors: SSCU, Indian Institute of Science, Bangalore, Karnataka, India.
authors: Krishna
authors: K
authors: Shrinivas
authors: SSCU, Indian Institute of Science, Bangalore, Karnataka, India.
authors: Biman
authors: B
authors: Bagchi
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007700:Kinetics; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D014807:Vitamin D