TY - JOUR
T1 - Dendritic cells ameliorate autoimmunity in the cns by controlling the homeostasis of PD-1 receptor+ regulatory T cells
AU - Yogev, Nir
AU - Frommer, Friederike
AU - Lukas, Dominika
AU - Kautz-Neu, Kordula
AU - Karram, Khalad
AU - Ielo, Daniele
AU - von Stebut, Esther
AU - Probst, Hans Christian
AU - van den Broek, Maries
AU - Riethmacher, Dieter
AU - Birnberg, Tal
AU - Blank, Thomas
AU - Reizis, Boris
AU - Korn, Thomas
AU - Wiendl, Heinz
AU - Jung, Steffen
AU - Prinz, Marco
AU - Kurschus, Florian C.
AU - Waisman, Ari
N1 - Funding Information:
We would like to thank I. Mufazalov, C. Steigerwald, and C. Couto Garcia for help and support in the performance of experiments and data analysis, and P. Adams, A. Heinen, and M. Snetkova for their excellent technical assistance. We are also very grateful to A. Young, J. Masri, and B. Becher for their careful correction of the manuscript. D.L. was supported by a fellowship from the Immunology Center of Excellence Mainz (FZI) and D.I. by a fellowship from the German Research Foundation (DFG) graduate school GRK 1043. This work was supported by the DFG grants WA 1600/3-1 and SFB/TR 52 to A.W., the DFG research group grant FOR1336 to A.W., S.J., and M.P, and by the German Ministry for Education and Research (BMBF, Consortium UNDERSTANDMS, as part of the “German Competence Network of MS”) to A.W., H.W., and M.P.
PY - 2012/8/24
Y1 - 2012/8/24
N2 - Mature dendritic cells (DCs) are established as unrivaled antigen-presenting cells (APCs) in the initiation of immune responses, whereas steady-state DCs induce peripheral T cell tolerance. Using various genetic approaches, we depleted CD11c+ DCs in mice and induced autoimmune CNS inflammation. Unexpectedly, mice lacking DCs developed aggravated disease compared to control mice. Furthermore, when we engineered DCs to present a CNS-associated autoantigen in an induced manner, we found robust tolerance that prevented disease, which coincided with an upregulation of the PD-1 receptor on antigen-specific T cells. Additionally, we showed that PD-1 was necessary for DC-mediated induction of regulatory T cells. Our results show that a reduction of DCs interferes with tolerance, resulting in a stronger inflammatory response, and that other APC populations could compensate for the loss of immunogenic APC function in DC-depleted mice.
AB - Mature dendritic cells (DCs) are established as unrivaled antigen-presenting cells (APCs) in the initiation of immune responses, whereas steady-state DCs induce peripheral T cell tolerance. Using various genetic approaches, we depleted CD11c+ DCs in mice and induced autoimmune CNS inflammation. Unexpectedly, mice lacking DCs developed aggravated disease compared to control mice. Furthermore, when we engineered DCs to present a CNS-associated autoantigen in an induced manner, we found robust tolerance that prevented disease, which coincided with an upregulation of the PD-1 receptor on antigen-specific T cells. Additionally, we showed that PD-1 was necessary for DC-mediated induction of regulatory T cells. Our results show that a reduction of DCs interferes with tolerance, resulting in a stronger inflammatory response, and that other APC populations could compensate for the loss of immunogenic APC function in DC-depleted mice.
UR - http://www.scopus.com/inward/record.url?scp=84865391725&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.05.025
DO - 10.1016/j.immuni.2012.05.025
M3 - Article
C2 - 22902234
AN - SCOPUS:84865391725
SN - 1074-7613
VL - 37
SP - 264
EP - 275
JO - Immunity
JF - Immunity
IS - 2
ER -
