Philip William Askenase MD

Professor of Medicine (Immunology)

Research Interests

exosomes; healing mesenchymal stem cell exosomes; neuropsychiatric diseases; poison ivy; multiple sclerosis; autism

Current Projects

Seeking to link these basic findings in mice with conditions in humans (asthma, atopic dermatitis), and to dissect out recent discovery that serum complement components, a system of more than 9 labile enzymatic and fragmenting proteins in the blood, also participate in these critical interactions leading to T cell recruitment in cell mediated immunity in vivo; role of RNA in a T cell suppressor factor relevant to hematopoietic cancers--cDNA cloning and identification of the RNA portion of the TsF, determining the biological properties of the cloned TsF RNA, towards eventual therapy of malignancies

Research Summary

The dissection of crucial cellular and molecular interactions guiding the traffic and eventual recruitment of antigen-specific T cells, out of the blood vessels, and into the tissues, at specific sites of immune reactivity, such as allergic responses (asthma) or protective responses, expulsion of helminth worms from the GI tract, or ticks from the skin.

Have identified that micro-mediators, such as serotonin and leukotrienes, released by mediator-containing cells, such as mast cells or platelets, are of crucial importance in alteration of the local vasculature to allow penetration into the tissues by antigen-specific T cells, that arrive and interact with local antigen-presenting cells that present relevant peptides of antigens, causing release of cytokines by the T cells, to mediate local inflammation and allergy, or in contrast, immune protection and resistance.

Extensive Research Description

T Cell Mediated Suppression via miRNA in Nanovesicle Exosomes Acting Between Cells.

An immensely exciting project in our laboratory stems from our recent discovery that a T cell suppressive factor (TsF) that inhibits effector Th1 and Th2 cells in vivo, contains an RNA that is a small, double-stranded RNA. We postulate it is a regulatory miRNA (likely in a pre-miRNA), that acts by being transported between cells; from the suppressive T cells to target effector T cells cells via exosomes [suppressor cell secreted nanovesicles (50-100nm) that contain proteins, RNA and miRNA] to suppress immune responses. The effect produced is systematic and thus endocrine in nature. Further, similar suppressive exosomes can be found in the blood serum of mice tolerized to induce the suppressive T cells that release supernatant of TsF RNA in exosomes, and clinically in the blood of patients with cancer, autoimunity, allergy etc. This cell to cell transfer, in a mammalian system. of active genetic information for immunoregulation is unprecedented and paradigm breaking.

It is likely that interference with this newly recognized mode of antigen-specific T cell suppression can be used therapeutically, or inhibited with antagomirs where indicated. Antagomirs could act to reverse suppressive miRNA in cancer. This also could create a new pathway in specific immunotherapy that could compliment existing non-specific treatments, resulting in less toxic side effects, greater specificity, and safer use of higher doses of current non-specific drugs (steroids) and biologics (anti-TNF etc). Alternatively, in vitro alteration of syngeneic exosomes for in vivo therapeutic use to alter immune responses, opens an entirely new avenue of possible immunotherapy. Finally, detection and analysis of exosomes in the blood is a new method of determining the patient’s immune response.

Selected Publications

  • 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.
  • Askenase PW, Majewska M, Kerfoot S, and Szczepanik M. Participation of NKT cells in the early and late components of Tc1 mediated contact sensitivity: Role of ??-T cells. Submitted 2009.
  • Askenase PW, Majewska M, and Szczepanik M. NK cell mediated contact sensitivity is elicitable 1 hour after immunization and depends on IFN-? and IL-12 production. Submitted 2009.
  • Ptak W, Majewska M, Bryniarski K, Ptak M, Lobo FM, Zajac K, Zemelka M, Askenase PW, and Szczepanik M. Epicutaneous immunization with protein antigen in the presence of TLR4 ligand induces TCR??+ CD4+ contrasuppressor T cells that reverse skin induced suppression of the Th1 mediated contact sensitivity responses. J. Immunol. 182:837-850, 2009.
  • Kerfoot S, Szczepanik M, Tung J, and Askenase P. Identification of initiator B-cells, a novel subset of activation induced deaminase (AID)-dependent B-1-like cells that mediate initiation of contact sensitivity. J Immunol. 181:1717-1727, 2008.
  • Pedra JH, Mattner J, Tao J, Kerfoot S, Davis RJ, Flavell RA, Askenase PW, Yin Z, and Fikrig E. c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infection. Infect Immun. 76(1):308-316, 2008.
  • Itakura A, Kikuchi Y, Kouro T, Ikutani M, Takaki S, Askenase PW, Takatsu K. Interleukin-5 plays an essential role in elicitation of contact sensitivity through dual effects on eosinophils and B-1 cells. Int. Arch. Allergy and Immunol. 140 (Suppl. 1):8-16, 2006.
  • Pedra JH, Mattner J, Tao J, Kerfoot S, Davis RJ, Flavell RA, Askenase PW, Yin Z, and Fikrig E. c-Jun NH2-terminal kinase 2 inhibits gamma interferon production during Anaplasma phagocytophilum infection. Infect Immun. 76(1):308-316, 2008.


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