2007 Off Campus Research Internship Awardee

Jasmine Shafagh (Biology)
(Concentration in Neural and Behavior Sciences)

Published Paper

Mentor: Dr. Jayasri Das Sarma

(Dept. of Neurology at Jefferson University)


Cytokines and Inflammatory diseases, such as MS --- Is there a Link?

Cytokines are secreted proteins that regulate many biological activities, and plays an important role in immunity. A new family of cytokines, IL-17, have been identified and reveal a distinct ligand-receptor signaling system. IL-17 is produced by a sub population of T-cells, Th17 cells. Th17 cells and IL-17 are the major encephalitogenic T cells and cytokines in the EAE. Functional analysis of IL-17 has demonstrated its ability to induce the production of other cytokines and chemokines, such as Il-6, IL-8, G-CSF, GM-CSF, MCP-1 from a variety of cell types. Functional studies have also provided evidence for the importance of IL-17 in the regulation of immune system, its promotion of chronic inflammatory response and Th2 responses. The cognate receptors for the IL-17 family identified thus far are: IL-17R, IL17RH-1. IL-17RL, IL17-RD, and IL-17RE. However, the ligand specificities of many of these receptors have not been established. The IL-17 signaling system is operative in disparate tissues such as articular cartilage, bone, meniscus, brain, hematopoietuc tissue, kidney, skin and intestine. Thus, the evolving IL-17 family of ligands and receptors may play an important role in the homeostasis of tissues in health and disease beyond the immune system. The IL-17 receptor is a Type 1 transmembrane glycoprotein, and shares 84 and 72% aa sequence identity with rat and human IL-17 R (receptor) respectively.

Our research study will be focused to determine the major site of action of IL-17 receptor in the EAE is in the central nervous system (CNS). In other words we will attempt to answer the question: do CNS cells express the IL-17R?

Our research will be as follows:

CNS cells specific localization of IL-17R protein in healthy vs. EAE mice by routine double label immunofluorescence.

Expression of IL-17R mRNA by RT-PCR

Expression of IL-17R protein in neonatal glial cells by Flow cytometry.

Co-culturing of Th1 vs. Th17 cells with neonatal astrocytes/microglia

  • alteration of the expression level of IL-17R

  • functional significance of differential expression and

  • measurement of downstream products (e.g. cytokines, chemokines).
Overall, we expect to verify that the CNS cells do express the IL-17R. Increased understanding of the role of complexity of the cytokine network, together with characterization of its receptor would help to uncover the molecular mechanisms of inflammatory diseases, such as MS.

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