Daniel Hawiger, M.D., Ph.D.
Molecular Microbiology and Immunology
M.D., University of Vienna Medical School, Vienna, Austria
Ph.D., Rockefeller University, New York, NY
Dendritic cells (DCs) have crucial roles in priming effector T cells but DCs also have critical tolerogenic functions in the peripheral immune system, extending the maintenance of immune homeostasis and blocking autoimmune responses. However, broad tolerogenic functions of DCs including induction of peripheral regulatory T cells (pTreg cells) could hamper protective immune responses against some pathogens and tumors, whereas an inadvertent activation of autoragressive T cells in the presence of pro-inflammatory stimuli could lead to autoimmunity. Therefore the maintenance of immune homeostasis by DCs requires specific mechanisms that actively adjust T cell functions to promote tolerance while preserving an overall high plasticity of the immune responses.
(DCs with specialized tolerogenic functions are represented here as red flowers attracting
naïve T cells depicted as green bees that can acquire regulatory functions, symbolized
as purple halos. Trends in Immunology, 2017, Nov;38(11):793-804) https://authors.elsevier.com/a/1VyH5_XTJFZQzX
Cover image by Htoi Jones.
To clarify the mechanisms by which DCs govern T cell tolerance in the context of autoimmune disorders such as multiple sclerosis (MS) but also other immune responses, studies in my laboratory are focused on the roles of specialized subsets of DCs and their specific functions in tolerance as well as the relevant molecular mechanisms induced by such DCs in T cells. Our work has elucidated the functions of specific immunomodulatory pathways, cell signaling regulators and transcription factors that establish tolerogenic outcomes of the interactions between T cells and DCs.
Labs and Facilities
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Postdoctoral Fellow email@example.com
Jacob G. Henderson, Ph.D.
(graduate student 2011-15)
Andrew J. Jones, Ph.D.
(M.D.,Ph.D. student 2013-17)
Selected Representative Publications
Iberg CA, Jones A and Hawiger D
Dendritic cells as inducers of peripheral tolerance.
Trends in Immunology, 2017, 38(11):793-804
Jones A and Hawiger D
Peripherally Induced Regulatory T Cells: Recruited Protectors of the Central Nervous System against Autoimmune Neuroinflammation
Frontiers in Immunology, 2017, 8:532
Jones A, Bourque J, Kuehm L, Opejin A, Teague RM , Gross C and Hawiger D
Immunomodulatory functions of BTLA and HVEM govern induction of extrathymic regulatory T cells and tolerance by dendritic cells.
Immunity, 2016, 45(5): p.1066-1077
Henderson JG and Hawiger D
Regulation of extrathymic Treg cell conversion by CD5.
Oncotarget, 2015, 6(29): p. 26554-555
Jones A, Opejin A, Henderson JG, Gross C, Jain R, Epstein JA, Flavell RA
and Hawiger D
Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That Require Hopx To Inhibit Intrinsic IL-2 Expression.
Journal of Immunology, 2015, 15;195(4): p. 1489-97
Henderson JG, Opejin A, Jones A, Gross C, and Hawiger D
CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens.
Immunity, 2015, 42(3): p. 471-483
Piccio L, Cantoni C, Jacob G., Henderson JG, Hawiger D, Ramsbottom M, Mikesell R, Ryu J, Hsieh
CS, Cremasco V, Haynes W, Dong LQ, Chan L, Galimberti D Cross AH,
Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis.
Eur J Immunol, 2013, 43(8): p. 2089-100.
Hawiger D, Wan YY, Eynon EE, Flavell RA
The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell-mediated peripheral T cell unresponsiveness.
Nature Immunology, 2010, 11(10): p. 962-8.
Hawiger D, Tran E, Du W, Booth CJ, Wen L, Dong C, Flavell RA
ICOS mediates the development of insulin-dependent diabetes mellitus in nonobese diabetic mice.
Journal of Immunology, 2008, 180(5): p. 3140-7.
Kretschmer K, Apostolou I, Hawiger D, Khazaie K, Nussenzweig MC, von Boehmer H
Inducing and expanding regulatory T cell populations by foreign antigen.
Nature Immunology, 2005, 6(12): p. 1219-27.
Hawiger D, Masilamani RF, Bettelli E, Kuchroo VK, Nussenzweig MC
Immunological unresponsiveness characterized by increased expression of CD5 on peripheral T cells induced by dendritic cells in vivo.
Immunity, 2004. 20(6): p. 695-705.
Steinman RM, Hawiger D, Nussenzweig MC
Tolerogenic dendritic cells.
Annual Review of Immunology, 2003, 21: p. 685-711.
Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig
Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo.
Journal of Experimental Medicine, 2001, 194(6): p. 769-79.