TY  - JOUR
A1  - Wajant, Harald
A1  - Beilhack, Andreas
T1  - Targeting regulatory T cells by addressing tumor necrosis factor and its receptors in allogeneic hematopoietic cell transplantation and cancer
JF  - Frontiers in Immunology
N2  - An intricate network of molecular and cellular actors orchestrates the delicate balance between effector immune responses and immune tolerance. The pleiotropic cytokine tumor necrosis factor-alpha (TNF) proves as a pivotal protagonist promoting but also suppressing immune responses. These opposite actions are accomplished through specialist cell types responding to TNF via TNF receptors TNFR1 and TNFR2. Recent findings highlight the importance of TNFR2 as a key regulator of activated natural FoxP3+ regulatory T cells (Tregs) in inflammatory conditions, such as acute graft-vs.-host disease (GvHD) and the tumor microenvironment. Here we review recent advances in our understanding of TNFR2 signaling in T cells and discuss how these can reconcile seemingly conflicting observations when manipulating TNF and TNFRs. As TNFR2 emerges as a new and attractive target we furthermore pinpoint strategies and potential pitfalls for therapeutic targeting of TNFR2 for cancer treatment and immune tolerance after allogeneic hematopoietic cell transplantation.
KW  - GVHD
KW  - graft vs. host disease
KW  - cancer
KW  - Tregs (regulatory T cells)
KW  - TNFR family costimulatory receptors
KW  - TNFR2 agonists
KW  - TNFR2 antagonism
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201578
VL  - 10
IS  - 2040
ER  - 
TY  - JOUR
A1  - Weiß, Emil
A1  - Ramos, Gustavo Campos
A1  - Delgobo, Murilo
T1  - Myocardial-Treg crosstalk: How to tame a wolf
JF  - Frontiers in Immunology
N2  - The immune system plays a vital role in maintaining tissue integrity and organismal homeostasis. The sudden stress caused by myocardial infarction (MI) poses a significant challenge for the immune system: it must quickly substitute dead myocardial with fibrotic tissue while controlling overt inflammatory responses. In this review, we will discuss the central role of myocardial regulatory T-cells (Tregs) in orchestrating tissue repair processes and controlling local inflammation in the context of MI. We herein compile recent advances enabled by the use of transgenic mouse models with defined cardiac antigen specificity, explore whole-heart imaging techniques, outline clinical studies and summarize deep-phenotyping conducted by independent labs using single-cell transcriptomics and T-cell repertoire analysis. Furthermore, we point to multiple mechanisms and cell types targeted by Tregs in the infarcted heart, ranging from pro-fibrotic responses in mesenchymal cells to local immune modulation in myeloid and lymphoid lineages. We also discuss how both cardiac-specific and polyclonal Tregs participate in MI repair. In addition, we consider intriguing novel evidence on how the myocardial milieu takes control of potentially auto-aggressive local immune reactions by shaping myosin-specific T-cell development towards a regulatory phenotype. Finally, we examine the potential use of Treg manipulating drugs in the clinic after MI.
KW  - Tregs (regulatory T cells)
KW  - Foxp3
KW  - myocardial infarction
KW  - heart
KW  - fibrosis
KW  - T-cells
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275591
SN  - 1664-3224
VL  - 13
ER  -