Daniel Hawiger, M.D., Ph.D.
Professor
Molecular Microbiology and Immunology
Education
M.D.: Vienna University
Ph.D.: Rockefeller University
Postdoctoral: Yale University
Research Interests
Dendritic cells (DCs) have crucial roles in priming effector T cells involved in immune
responses against pathogens and tumors. DCs also extend the maintenance of immune
homeostasis by blocking autoimmune T-cell responses relevant to autoimmune diseases.
My laboratory studies these functions of DCs and the resultant differentiation of T cells relevant to regulation of immune responses in health and disease. Our work has uncovered specific mechanisms that establish outcomes of the interactions between T cells and DCs resulting in T cell tolerance: a) relevant molecular mechanisms of CD5, a specific regulator of T cell signaling (Immunity. 2015 Mar 17;42(3):471-83. DOI: 10.1016/j.immuni.2015.02.010), b) Homeodomain only protein (Hopx), a transcription co-factor, orchestrating homeostasis of the de novo induced regulatory T cells, J Immunol. 2015 Aug 15;195(4):1489-97. DOI: 10.4049/jimmunol.1500174), and c) B and T lymphocyte attenuator (BTLA), a key immunomodulator facilitating the de novo induction of regulatory T cells (Immunity. 2016 Nov 15;45(5):1066-1077. DOI: 10.1016/j.immuni.2016.10.008).
Tumor necrosis factor alpha (TNF-α) is involved in various pathologic states including autoimmunity. Most recently, we revealed that sensing of TNF-α by DCs involved in tolerance leads to acute death of such tolerogenic DCs in vivo (Cell Rep. 2022 Apr 12;39(2):110657. DOI: 10.1016/j.celrep.2022.110657). This finding may be directly relevant for the design of new vaccines and immunotherapies. Such immunotherapies can also utilize a specific delivery of antigens and other molecules to DCs by specifically designed antibody-like molecules as outlined in (Antibodies (Basel). 2022 Jan 25;11(1):8. DOI: 10.3390/antib11010008).
A key turning point in the development of autoimmune disease including multiple sclerosis
(MS) is the formation of T cells that are poised for subsequent autoimmune effector
differentiation. We clarified how DCs can contribute to this process under homeostatic
conditions by inducing antigen-specific “pre-effector” T cells with autoimmune potential
(Cell Rep. 2020 Nov 24;33(8):108424. DOI: 10.1016/j.celrep.2020.108424). This finding may help to establish approaches for tracking the early development
of autoimmune processes, also resulting in new specific targets for novel immunotherapies.