Philip William Askenase MD
Professor of Medicine (Immunology)
Departments & Organizations
Our focus is newly recognized extracellular nanovesicles called exosomes (100 nanometers across; one 500th the size of cells) that are made by all cells, present in all fluids and made in some form by all species down to and including bacteria and fungi. Remarkably, they transfer small RNAs between cells, particularly miRNAs, to then function genetically in the acceptor cells. Our system has been CD8+ suppressor T cells that make antigen specific exosomes due to a coating of immunoglobulin light chains that are induced by antigen high dose tolerance to suppress effector T cells. Our initial system was the mouse model of allergic cutaneous contact hypersensitivity dermatitis (poison ivy), but now has been extended to delayed-type hypersensitivity (DTH) to the protein antigen ovalbumin. A remarkable aspect of this system is that these tiny vesicles that contain only 0.2 attoliters carry miRNA at zeptomolar concentration to function in vivo in an endocrine manner to genetically alter the function of distant effector T cells at the site of active responses. This new cell to cell communication system, that seems fundamental to life, has led us to now investigate exosome treatment by the intranasal route where the vesicles cross the dorsal anterior sinus cribriform plate to then pass the blood barrier and strongly inhibit the mouse model of autoimmune multiple sclerosis. Further, we are contemplating use of healing mesenchymal stem cell exosomes for similar treatment of neuropsychiatric diseases, such as autism. It is interesting that basic allergy research on poison ivy has led to consideration of entirely new therapies for multiple sclerosis and autism. more...
- M.D., Yale University, 1965
- Bryniarski K, Ptak W, Jayakumar A, Tuschl T, Hafner M, Püllmann K, Caplan M, Chairoungdua A, Lu J, Adams B, Sikora E, Nazimek K, Marquez S, Kleinstein SH, Sangwung, P, Iwakiri Y, Delgato E, Redegeld F, Wojcikowski J, Wladyslawa Daniel A, Groot Kormelink T, and Askenase PW. Antibody light chain coated antigen specific exosomes deliver suppressor T cell-derived miRNA-150 to inhibit effector T cells. J Allergy Clin Immunol. 2013 Jul;132(1):170-81. doi:10.1016/j.jaci.2013.04.048.
- Yamamoto N, Kerfoot S, and Askenase PW. Role of B-1 cells in early acquired protection from pneumococcal pneumonia: Immune B-1 cells reconstitute defective protection on AID-/- mice. Submitted 2009
- Dey N, Szczepanik M, Lau K, Majewska M, and Askenase P. Hepatic lipids isolated 30 minutes after cutaneous contact sensitization activate naïve iNKT cells in vitro in a CD1d-dependent fashion. Submitted 2009.