Interleukin-21 and the relationship with the Th1/Th17 axis Adria Carbo – Lab Meeting Presentation March 15 th 2013
Interleukin-21 Interleukin 21 (IL-21) is mostly produced by activated CD4+ T cells (especially Th17), T follicular helper cells and NKT cells. IL-21 induces proliferation and increases cell survival and cytokine synthesis in T cells. IL-21 helps to the maintenance of Th17 by acting in an autocrine fashion. IL-21 inhibits IL-2 production and impairs Treg homeostasis IL-21 is increased with H. pylori infection and correlates with levels of gastritis in the mouse model. IL-21 was associated with H. pylori infection in a study of infected humans
MIEP and Vanderbilt University Experimental work Computational work
IL-21 and H. pylori wild type IL-21 null Mathematical Modeling & Pathway Analysis Flow cytometry, RT-PCR, Histopathology, Bacterial counts RESULTS
IL-21 and H. pylori
Calibration process ExperimentObjective Value Root Mean Square Error MeanError Mean Std. Deviation Experiment_2 (IL17) Experiment_3 (IFNg)
In silico simulations
AB
IL-10 is upregulated in IL-21 null mice
Side-by-side comparison
Conclusions Our results support that CD4+ are a crucial player for the development of H. pylori-associated gastritis IL-21 is not only required for the maintenance of IL-17 but also plays an important role in the development of the IFN response. IL-21 is not required at the first stage of differentiation, but plays a key role in a later stage of Th17 differentiation. IL-21 may be involved in controlling the balance of the regulatory versus effector responses during H. pylori. Our modeling results oriented the experimental analysis and set up. IL-21 can be a promising therapeutic target for treatment of T cell mediated diseases
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