My lab is focused on understanding the biology of dendritic cells (DCs) and T cells and their roles in autoimmunity. In one area of investigation, we have been determining the contributions of dendritic cells and inflammatory monocytes in the development and maintenance of EAE and assessing the implications for Multiple Sclerosis. We are currently undertaking studies to assess the significance of two different signaling pathways (FLT3 and KLF) in the function of these immune cells in EAE. We have generated data that indicate that myeloid derived cells play a significant role in the pathogenesis of EAE and that they may be novel targets for development of therapeutic approaches.
In the development of autoimmunity, polarization of T cell responses appears to be one method by which T cells become detrimental. Understanding the process by which T cells mature from naive cells into specific cell subtypes will be critical for understanding mechanisms of disease development. We have recently shown that the transcription factor KFL4 is required for the development of IL-17 responses by T cells and for the development of the autoimmune model EAE. We are currently determining mechanisms by which harmful Th17 responses develop and the pathways that lead to their initiation.
Additionally, we are investigating the ability of mesenchymal stem cells to modulate autoimmune responses. While previous results have shown that these stem cells can dampen harmful autoimmune responses, the mechanism by which this suppression occurs has not been elucidated. We are undertaking studies to determine methods by which MSCs impact on T cell development and polarization.
Lebson L, Gocke A, Rosenzweig J, Alder J, Civin C, Calabresi PA, Whartenby KA The transcription factor Kruppel-like Factor 4 (KLF4) regulates the differentiation of Th17 cells independently of RORt. Cutting Edge, Journal of Immunology, epub Nov 15 2010.
Wang T, Jiang Q, Chan C, Gorski K, McCadden E, Kardian D, Pardoll D, Whartenby KA. Inhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINOR. 2009 Mar 26;113(13):2906-13. Epub 2009 Jan 22.
Skarica M, Wang T, McCadden E, Kardian D, Calabresi PA, Small D, Whartenby KA Signal transduction inhibition of antigen presenting cells diminishes Th17 and Th1 responses in EAE. Journal of Immunology. 2009 Apr 1;182(7):4192-9.
Whartenby KA, Calabresi PA, Small D. FLT3 inhibitors for the treatment of autoimmune disease. Exp Opinion Invest Drugs, 2008; 2008 Nov;17(11):1685-92.