TY  - JOUR
A1  - Soehnlein, Oliver
A1  - Drechsler, Maik
A1  - Döring, Yvonne
A1  - Lievens, Dirk
A1  - Hartwig, Helene
A1  - Kemmerich, Klaus
A1  - Ortega-Gómez, Almudena
A1  - Mandl, Manuela
A1  - Vijayan, Santosh
A1  - Projahn, Delia
A1  - Garlichs, Christoph D.
A1  - Koenen, Rory R.
A1  - Hristov, Mihail
A1  - Lutgens, Esther
A1  - Zernecke, Alma
A1  - Weber, Christian
T1  - Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes
JF  - EMBO Molecular Medicine
N2  - We used a novel approach of cytostatically induced leucocyte depletion and subsequent reconstitution with leucocytes deprived of classical \((inflammatory/Gr1^{hi})\) or non-classical \((resident/Gr1^{lo})\) monocytes to dissect their differential role in atheroprogression under high-fat diet (HFD). Apolipoprotein E-deficient \((Apoe^{-/-})\) mice lacking classical but not non-classical monocytes displayed reduced lesion size and macrophage and apoptotic cell content. Conversely, HFD induced a selective expansion of classical monocytes in blood and bone marrow. Increased CXCL1 levels accompanied by higher expression of its receptor CXCR2 on classical monocytes and inhibition of monocytosis by CXCL1-neutralization indicated a preferential role for the CXCL1/CXCR2 axis in mobilizing classical monocytes during hypercholesterolemia. Studies correlating circulating and lesional classical monocytes in gene-deficient \(Apoe^{-/-}\) mice, adoptive transfer of gene-deficient cells and pharmacological modulation during intravital microscopy of the carotid artery revealed a crucial function of CCR1 and CCR5 but not CCR2 or \(CX_3CR1\) in classical monocyte recruitment to atherosclerotic vessels. Collectively, these data establish the impact of classical monocytes on atheroprogression, identify a sequential role of CXCL1 in their mobilization and CCR1/CCR5 in their recruitment.
KW  - hypercholeterolemia
KW  - CCR2
KW  - atherosclerosis
KW  - chemokine
KW  - accumulation
KW  - subsets
KW  - inflammatory sites
KW  - fractalkine
KW  - marcophages
KW  - mobilization
KW  - monocyte
KW  - recruitment
KW  - bone-marrow
KW  - atheriosclerotic lesions
KW  - hyperlipedemic mice
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122204
SN  - 1757-4676
VL  - 5
ER  - 
TY  - JOUR
A1  - Feigl, Frederik Fabian
A1  - Stahringer, Anika
A1  - Peindl, Matthias
A1  - Dandekar, Gudrun
A1  - Koehl, Ulrike
A1  - Fricke, Stephan
A1  - Schmiedel, Dominik
T1  - Efficient redirection of NK cells by genetic modification with chemokine receptors CCR4 and CCR2B
JF  - International Journal of Molecular Sciences
N2  - Natural killer (NK) cells are a subset of lymphocytes that offer great potential for cancer immunotherapy due to their natural anti-tumor activity and the possibility to safely transplant cells from healthy donors to patients in a clinical setting. However, the efficacy of cell-based immunotherapies using both T and NK cells is often limited by a poor infiltration of immune cells into solid tumors. Importantly, regulatory immune cell subsets are frequently recruited to tumor sites. In this study, we overexpressed two chemokine receptors, CCR4 and CCR2B, that are naturally found on T regulatory cells and tumor-resident monocytes, respectively, on NK cells. Using the NK cell line NK-92 as well as primary NK cells from peripheral blood, we show that genetically engineered NK cells can be efficiently redirected using chemokine receptors from different immune cell lineages and migrate towards chemokines such as CCL22 or CCL2, without impairing the natural effector functions. This approach has the potential to enhance the therapeutic effect of immunotherapies in solid tumors by directing genetically engineered donor NK cells to tumor sites. As a future therapeutic option, the natural anti-tumor activity of NK cells at the tumor sites can be increased by co-expression of chemokine receptors with chimeric antigen receptors (CAR) or T cell receptors (TCR) on NK cells can be performed in the future.
KW  - chemokine receptor
KW  - migration
KW  - immune cell infiltration
KW  - trafficking
KW  - NK cells
KW  - immunotherapy
KW  - CCR2
KW  - CCR4
KW  - genetic engineering
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304049
SN  - 1422-0067
VL  - 24
IS  - 4
ER  -