Heather Walk
e-mail address: hgrifka@umich.edu

Mentor: Benjamin Segal, MD

Research Description:

Experimental autoimmune encephalitis (EAE) is a rodent model for human multiple sclerosis mediated by myelin-specific CD4+ T cells. Our lab has demonstrated that CD4+ T cells polarized toward IFN-g-producing Th1 cells or IL-17-producing Th17 cells are able to induce disease with clinically similar yet histologically distinct effects. T-bet is a transcription factor expressed by multiple cell types, but is most widely known for its role in regulating IFN-g expression and is critical for Th1 development. Mice deficient in T-bet are protected from EAE during active immunization or by adoptive transfer of myelin-reactive T cells polarized with IL-12 or cultured with myelin peptide alone. Furthermore, recent data suggests that T-bet levels are upregulated in both Th1 and Th17 encephalitogenic T cells and that silencing T-bet downregulates IL-17 and IL-23R expression, both of which are critical for Th17 development. However, if T-bet expression is critical for encephalitogenicity, we expected myelin-specific T-bet knockout cells polarized with IL-23 to produce T-bet KO Th17 cells would not cause disease upon transfer into WT hosts. Unexpectedly, mice receiving T-bet knockout Th17 cells did acquire disease, and the mice frequently relapse with an atypical form of the disease. My research focuses on this unique phenotype and characterization of the effector cells involved. This will offer insights into the role of T-bet in T helper cell function and T-cell mediated autoimmunity.

Publications:


Abstracts:

Lee AW, Grifka H, Yu S. (2008) Gab2 Is a Key Determinant
of Mononuclear Phagocyte Development and a Regulator of Macrophage
Recruitment in Acute Inflammation. BLOOD. 50th Annual Meeting of the
American Society of Hematology

Lee AW, States DJ, Grifka H. (2007) Essential role of GAB2 in CSF-1
dependent macrophage development in the bone marrow. BLOOD. 49th
Annual Meeting of the American Society of Hematology.

Awards:

Rackham Merit Fellowship