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  - Rauschenberger, Tabea
A1  - Schmitt, Viola
A1  - Azeem, Muhammad
A1  - Klein-Hessling, Stefan
A1  - Murti, Krisna
A1  - Grän, Franziska
A1  - Goebeler, Matthias
A1  - Kerstan, Andreas
A1  - Klein, Matthias
A1  - Bopp, Tobias
A1  - Serfling, Edgar
A1  - Muhammad, Khalid
T1  - T cells control chemokine secretion by keratinocytes
JF  - Frontiers in Immunology
N2  - The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8\(^+\)T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8\(^+\)T cells. One key molecule is IFN-γ that is synthesized by CD8\(^+\)T cells under the control of NFATc1 and NFATc2. CD8\(^+\)T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8\(^+\)T cells induced numerous type I IFN-inducible “defense genes” in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level.
KW  - chemokine
KW  - keratinocytes
KW  - IFN
KW  - lichen planus
KW  - T cells
KW  - Nfatc1
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195695
SN  - 1664-3224
VL  - 10
IS  - 1917
ER  -