Search

Glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR, TNFRSF18, and CD357) is expressed at high levels in activated T cells and regulatory T cells (Tregs). In this review, we present data from mouse and human studies suggesting that GITR is a crucial player in the differentiation of thymic Tregs (tTregs), and expansion of both tTregs and peripheral Tregs (pTregs). The role of GITR in Treg expansion is confirmed by the association of GITR expression with markers of memory T cells. In this context, it is not surprising that GITR appears to be a marker of active Tregs, as suggested by the association of GITR expression with other markers of Treg activation or cytokines with suppressive activity (e.g., IL-10 and TGF-β), the presence of GITR+ cells in tissues where Tregs are active (e.g., solid tumours), or functional studies on Tregs. Furthermore, some Treg subsets including Tr1 cells express either low or no classical Treg markers (e.g., FoxP3 and CD25) and do express GITR. Therefore, when evaluating changes in the number of Tregs in human diseases, GITR expression must be evaluated. Moreover, GITR should be considered as a marker for isolating Tregs. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on the topic pertaining to the role of GITR cells in immune homeostasis.

Aims Spinal cord injury ( SCI) occurs following damage to the spinal column. Following trauma, tissue damage is further exacerbated by a secondary damage due to a SCI-activated inflammatory process. Control of leukocytes activity is essential to therapeutic inhibition of the spinal cord damage to ameliorate the patient's conditions. The mechanisms that regulate neuroinflammation following SCI, including T-cell infiltration, have not been completely clarified. Glucocorticoids ( GC) are antiinflammatory drugs widely used in therapy, including treatment of SCI. GC efficacy may be linked to many molecular mechanisms that are involved in regulation of leukocytes migration, activation, and differentiation. We have previously shown that the antiinflammatory activity of GC is in part mediated by glucocorticoid-induced leucine zipper ( GILZ). Here, we investigated the role of GILZ in inflammation and spinal cord tissue damage following a spinal trauma. Methods We address the role of GILZ in SCI-induced inflammation and tissue damage using a model of SCI in gilz knockout (gilz KO) and wild-type ( WT) mice. Results We found that GILZ deficiency is associated with a strong reduction of SCI-induced inflammation and a significantly reduced lesion area following SCI. Conclusion These results demonstrate that GILZ is involved in induction of neuroinflammation and functional outcomes of spinal cord trauma. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are steroid hormones produced by the adrenal gland and regulated by the hypothalanms-pituitary-adrenal axis. GCs mediate effects that mostly result in transcriptional regulation of glucocorticoid receptor target genes. Mitogen-activated protein kinases (MAPKs) comprise a family of signaling proteins that convert extracellular stimuli into the activation of intracellular transduction pathways via phosphorylation of a cascade of substrates. They modulate a variety of physiological cell processes, such as proliferation, apoptosis, and development. However, when MAPKs are improperly activated by proinflammatory and/or extracellular stress stimuli, they contribute to the regulation of proinflammatory transcription factors, thus perpetuating activation of the inflammatory cascade. One of the mechanisms by which GCs exert their anti-inflammatory effects is negative interference with MAPK signaling pathways. Several functional interactions between GCs and MAPK signaling have been discovered and studied Some of these interactions involve the GC-mediated up-regulation of proteins that in turn interfere with the activation of MAPK, such as ghicocorticoid-induced-leucine zipper, MAPK phosphatase- 1, and annexin-1. Other mechanisms include activated GR directly interacting with components of the MAPK pathway and negatively regulating their activation. The multiple interactions between GCs and MAP pathways and their potential biological relevance in mediating the anti-inflammatory effects of GCs are reviewed. [ABSTRACT FROM AUTHOR]