TCR signaling inhibits glucocorticoid-induced apoptosis in murine thymocytes depending on the stage of development

Erlacher, Miriam; Knoflach, Michael; Stec, Ilona E.M.; Böck, Günther; Wick, Georg; Wiegers, G. Jan

doi:10.1002/eji.200526279

Cited by 27 publications

(24 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since these early (within 4 h) events were not antagonised by the GC antagonist pretreatment, the possibility of non-genomic GC action arises. Here, we found that apoptosis induced 12-24 h after a single high dose GC analogue exposure was inhibited by GC antagonist pretreatment, that is in line with previous findings by others (Erlacher et al, 2005).…”

Section: Discussionsupporting

confidence: 93%

Low glucocorticoid receptor (GR), high Dig2 and low Bcl-2 expression in double positive thymocytes of BALB/c mice indicates their endogenous glucocorticoid hormone exposure

et al. 2006

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 93%

Low glucocorticoid receptor (GR), high Dig2 and low Bcl-2 expression in double positive thymocytes of BALB/c mice indicates their endogenous glucocorticoid hormone exposure

et al. 2006

View full text Add to dashboard Cite

“…Apparently, due to the high local levels of proinflammatory cytokines, pronounced activation-induced cell death occurs during chronic EAE in the spinal cord of C57BL/6 mice, possibly mediated through Fas or galectin-1 (39). This can be expected to selectively counteract GC-induced apoptosis in the CNS but not in peripheral T cells (28,40). Therefore, we believe that GC-induced apoptosis in EAE and MS primarily pertains to peripheral T cells, at least under conditions of fulminant CNS inflammation.…”

Section: Discussionmentioning

confidence: 99%

Peripheral T Cells Are the Therapeutic Targets of Glucocorticoids in Experimental Autoimmune Encephalomyelitis

Wüst

Brandt

Tischner

et al. 2008

The Journal of Immunology

170

191

View full text Add to dashboard Cite

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 TH17 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.

show abstract

“…Furthermore it was observed that thymic endothelial cells produce GCs locally [49,50]. A 'mutual antagonism' model had therefore been suggested for thymocyte selection [51,52]. Thymocytes expressing TCRs with high avidity for selfpeptides/MHC undergo apoptosis due to the strong TCR signal that cannot be overruled by the GR signal.…”

Section: T Cellsmentioning

confidence: 99%

The role of the glucocorticoid receptor in inflammation and immunity

Baschant

Tuckermann

2010

The Journal of Steroid Biochemistry and Molecular Biology

306

212

View full text Add to dashboard Cite

TCR signaling inhibits glucocorticoid-induced apoptosis in murine thymocytes depending on the stage of development

Cited by 27 publications

References 47 publications

Low glucocorticoid receptor (GR), high Dig2 and low Bcl-2 expression in double positive thymocytes of BALB/c mice indicates their endogenous glucocorticoid hormone exposure

Low glucocorticoid receptor (GR), high Dig2 and low Bcl-2 expression in double positive thymocytes of BALB/c mice indicates their endogenous glucocorticoid hormone exposure

Peripheral T Cells Are the Therapeutic Targets of Glucocorticoids in Experimental Autoimmune Encephalomyelitis

The role of the glucocorticoid receptor in inflammation and immunity

Contact Info

Product

Resources

About