Reichardt, Holger Michael

[["dc.bibliographiccitation.artnumber","e0190846"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Meers, Garrit K."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Reichardt, Holger M."],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Reichardt, Sybille D."],["dc.date.accessioned","2019-07-09T11:45:08Z"],["dc.date.available","2019-07-09T11:45:08Z"],["dc.date.issued","2018"],["dc.description.abstract","Inflammatory bowel disease (IBD) is a highly prevalent intestinal disorder for which no cure exists. Currently, the standard first-line treatment of IBD consists of systemic glucocorticoid (GC) application, even though therapy can be complicated by unresponsiveness or adverse effects. In view of the importance of macrophages and neutrophils for the pathogenesis of IBD we set out to define the relevance of these cell types as targets of GC using the mouse model of DSS-induced colitis. We found that the disease did not resolve in GRlysM mice lacking the GC receptor (GR) in myeloid cells after removal of the chemical insult. While clinical symptoms and tissue damage in the colon ameliorated again in GRflox mice, the disease further aggravated in GRlysM littermates. The observed difference coincided with an increased abundance of macrophages in inflammatory infiltrates in the colon of mutant mice whereas neutrophil and T cell numbers were similar. Concomitantly, systemic IL-6 secretion and mRNA levels of pro-inflammatory cytokines in the colon were elevated in GRlysM mice and gene expression of scavenger receptors and IL-10 was diminished. Taken together, our results reveal an important role of myeloid cells as targets of GC in DSS-induced colitis and probably in IBD in humans as well."],["dc.identifier.doi","10.1371/journal.pone.0190846"],["dc.identifier.pmid","29324769"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15039"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59164"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Colitis"],["dc.subject.mesh","Colon"],["dc.subject.mesh","Dextran Sulfate"],["dc.subject.mesh","Disease Models, Animal"],["dc.subject.mesh","Interleukin-10"],["dc.subject.mesh","Interleukin-6"],["dc.subject.mesh","Intestinal Mucosa"],["dc.subject.mesh","Mice, Inbred C57BL"],["dc.subject.mesh","Mice, Transgenic"],["dc.subject.mesh","Myeloid Cells"],["dc.subject.mesh","RNA, Messenger"],["dc.subject.mesh","Receptors, Glucocorticoid"],["dc.title","Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid receptor in myeloid cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8434"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of immunology (Baltimore, Md. : 1950)"],["dc.bibliographiccitation.lastpage","8443"],["dc.bibliographiccitation.volume","180"],["dc.contributor.author","Wüst, Simone"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Kleiman, Anna"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2019-07-10T08:13:33Z"],["dc.date.available","2019-07-10T08:13:33Z"],["dc.date.issued","2008"],["dc.description.abstract","High-dose glucocorticoid (GC) therapy is widely used to treat multiple sclerosis (MS), but the underlying mechanisms remain debatable. In this study, we investigated the impact of GC administration on experimental autoimmune encephalomyelitis using different GC receptor (GR)-deficient mutants. Heterozygous GR knockout mice were less sensitive to dexamethasone therapy, indicating that the expression level of the receptor determines therapeutic efficacy. Mice reconstituted with homozygous GR knockout fetal liver cells showed an earlier onset of the disease and were largely refractory to GC treatment, indicating that the GR in hematopoietic cells is essential for the beneficial effects of endogenous GCs and dexamethasone. Using cell-type specific GR-deficient mice, we could demonstrate that GCs mainly act on T cells, while modulation of macrophage function was largely dispensable in this context. The therapeutic effects were achieved through induction of apoptosis and down-regulation of cell adhesion molecules in peripheral T(H)17 and bystander T cells, while similar effects were not observed within the spinal cord. In addition, dexamethasone inhibited T cell migration into the CNS, confirming that peripheral but not CNS-residing T lymphocytes are the essential targets of GCs. Collectively, our findings reveal a highly selective mechanism of GC action in experimental autoimmune encephalomyelitis and presumably multiple sclerosis."],["dc.identifier.pmid","18523311"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6206"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61275"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0022-1767"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Apoptosis"],["dc.subject.mesh","Blood-Brain Barrier"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Dexamethasone"],["dc.subject.mesh","Down-Regulation"],["dc.subject.mesh","Drug Delivery Systems"],["dc.subject.mesh","Encephalomyelitis, Autoimmune, Experimental"],["dc.subject.mesh","Female"],["dc.subject.mesh","Glycoproteins"],["dc.subject.mesh","Intercellular Signaling Peptides and Proteins"],["dc.subject.mesh","Leukocytes"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred C57BL"],["dc.subject.mesh","Mice, Knockout"],["dc.subject.mesh","Mice, Transgenic"],["dc.subject.mesh","Peptide Fragments"],["dc.subject.mesh","Receptors, Glucocorticoid"],["dc.subject.mesh","T-Lymphocyte Subsets"],["dc.subject.mesh","T-Lymphocytes, Regulatory"],["dc.title","Peripheral T cells are the therapeutic targets of glucocorticoids in experimental autoimmune encephalomyelitis."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]