TY  - JOUR
A1  - Schmid, Tobias
A1  - Falter, Lena
A1  - Weber, Sabine
A1  - Müller, Nils
A1  - Molitor, Konstantin
A1  - Zeller, David
A1  - Weber-Steffens, Dorothea
A1  - Hehlgans, Thomas
A1  - Wajant, Harald
A1  - Mostböck, Sven
A1  - Männel, Daniela N.
T1  - Chronic inflammation increases the sensitivity of mouse Treg for TNFR2 costimulation
JF  - Frontiers in Immunology
N2  - TNF receptor type 2 (TNFR2) has gained attention as a costimulatory receptor for T cells and as critical factor for the development of regulatory T cells (Treg) and myeloid suppressor cells. Using the TNFR2-specific agonist TNCscTNF80, direct effects of TNFR2 activation on myeloid cells and T cells were investigated in mice. \(In\) \(vitro\), TNCscTNF80 induced T cell proliferation in a costimulatory fashion, and also supported \(in\) \(vitro\) expansion of Treg cells. In addition, activation of TNFR2 retarded differentiation of bone marrow-derived immature myeloid cells in culture and reduced their suppressor function. \(In\) \(vivo\) application of TNCscTNF80-induced mild myelopoiesis in naïve mice without affecting the immune cell composition. Already a single application expanded Treg cells and improved suppression of CD4 T cells in mice with chronic inflammation. By contrast, multiple applications of the TNFR2 agonist were required to expand Treg cells in naïve mice. Improved suppression of T cell proliferation depended on expression of TNFR2 by T cells in mice repeatedly treated with TNCscTNF80, without a major contribution of TNFR2 on myeloid cells. Thus, TNFR2 activation on T cells in naïve mice can lead to immune suppression \(in\) \(vivo\). These findings support the important role of TNFR2 for Treg cells in immune regulation.
KW  - molecular medicine
KW  - inflammation
KW  - immune regulation
KW  - costimulation
KW  - MDSC
KW  - TNFR2
KW  - regulatory T cell
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173259
VL  - 8
ER  -