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  - 
TY  - JOUR
A1  - Krakow, Sören
A1  - Crescimone, Marie L.
A1  - Bartels, Charlotte
A1  - Wiegering, Verena
A1  - Eyrich, Matthias
A1  - Schlegel, Paul G.
A1  - Wölfl, Matthias
T1  - Re-expression of CD14 in response to a combined IL-10/TLR stimulus defines monocyte-derived cells with an immunoregulatory phenotype
JF  - Frontiers in Immunology
N2  - Interleukin 10 is a central regulator of the antigen-presenting function of myeloid cells. It exerts immunomodulatory effects in vivo and induces a regulatory phenotype in monocyte-derived cells in vitro. We analyzed phenotype and function of monocytic cells in vitro in relation to the cytokine milieu and the timing of TLR-based activation. In GM-CSF/IL-4 cultured human monocytic cells, we identified two, mutually exclusive cell populations arising from undifferentiated cells: CD83\(^+\) fully activated dendritic cells and CD14\(^+\) macrophage like cells. Re-expression of CD14 occurs primarily after a sequential trigger with a TLR signal following IL-10 preincubation. This cell population with re-expressed CD14 greatly differs in phenotype and function from the CD83+ cells. Detailed analysis of individual subpopulations reveals that exogenous IL-10 is critical for inducing the shift toward the CD14\(^+\) population, but does not affect individual changes in marker expression or cell function in most cases. Thus, plasticity of CD14 expression, defining a subset of immunoregulatory cells, is highly relevant for the composition of cellular products (such as DC vaccines) as it affects the function of the total product.
KW  - regulatory dendritic cells
KW  - MDSC
KW  - monocyte-derived DC
KW  - IL-10
KW  - macrophages
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201537
VL  - 10
IS  - 1484
ER  -