Glucocorticoid-induced TNFR-Related (GITR) protein is a member of the tumor necrosis factor receptor superfamily that modulates acquired and natural immune response. It is expressed in several cells and tissues, including T cells, natural killer cells, and, at lower levels, in cells of innate immunity. GITR is activated by its ligand, GITRL, mainly expressed on antigen presenting and endothelial cells. Recent evidence suggests that the GITR/GITRL system participates in the development of inflammatory responses, including shock, either due to early response of neutrophils and macrophages, or together with autoimmune/allergic pathogenesis. The pro-inflammatory role of the GITR/GITRL system is due to: 1) modulation of the extravasation process, 2) activation of innate immunity cells, 3) activation of effector T cells also favored by partial inhibition of suppressor T cells and modulation of dendritic function. This review summarizes the in vivo role of the GITR/GITRL system in inflammation and shock, explaining the mechanisms responsible for their effects, considering the interplay among the different cells of the immune system and transduction pathways activated by GITR and GITRL triggering. The hidden aspects about GITR/GITRL function, crucial for treatment planning of inflammatory diseases and shock by modulation of this system is stressed.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901298 | PMC |
| http://dx.doi.org/10.1100/tsw.2007.106 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC.
Front Immunol
January 2024
Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary.
Introduction: Tobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC).
Methods: Smoker controls without chronic illness were recruited as controls.
GITR/GITRL reverse signalling modulates the proliferation of hepatic progenitor cells by recruiting ANXA2 to phosphorylate ERK1/2 and Akt.
Cell Death Dis
April 2022
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Hepatic stem/progenitor cells are the major cell compartment for tissue repair when hepatocyte proliferation is compromised in chronic liver diseases, but the expansion of these cells increases the risk of carcinogenesis. Therefore, it is essential to explore the pathways restricting their expansion and abnormal transformation. The ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL) showed the most highly increased expression in hepatic progenitor cells treated with transforming growth factor (TGF)-β1.
View Article and Find Full Text PDFBiological role of GITR/GITRL in attributes and immune responses of macrophage.
J Leukoc Biol
February 2020
Department of Clinical Laboratory, the Second Hospital of Jilin University, Changchun, Jilin, P.R. China.
Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL), a member of the tumor necrosis factor superfamily, is expressed in APCs and acts as a costimulatory molecule in the immune system. Although the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR)/GITRL system has been modulated to promote or decrease T cell-related responses in multiple diseases, studies in macrophages are limited. To address this issue, we compared the expression of GITRL in various types of macrophages and analyzed whether GITRL can affect the fundamental properties and major functions of these cells.
View Article and Find Full Text PDFGlucocorticoid-induced TNFR-related gene (GITR) as a therapeutic target for immunotherapy.
Expert Opin Ther Targets
September 2018
a Department of Medicine , University of Perugia, Perugia , Italy.
Triggering of the glucocorticoid-induced TNFR-related gene (GITR) increases the activation of T lymphocytes and other immune system cells; furthermore, its ligand, GITRL, delivers signals in the cells where it is expressed. Areas covered: This review describes the effects of GITR/GITRL triggering/inhibition in conventional T cells, regulatory T cells (Tregs), monocytes/macrophages, endothelial cells and other cells of the immune system. GITR triggering appears to be an approach for promoting tumor rejection, treating infection and boosting vaccinations in several murine models.
View Article and Find Full Text PDFCo-stimulatory molecules in and beyond co-stimulation - tipping the balance in atherosclerosis?
Thromb Haemost
November 2011
Institute for Cardiovascular Prevention, Ludwig-Maximilians University Munich, Munich, Germany.
A plethora of basic laboratory and clinical studies has uncovered the chronic inflammatory nature of atherosclerosis. The adaptive immune system with its front-runner, the T cell, drives the atherogenic process at all stages. T cell function is dependent on and controlled by a variety of either co-stimulatory or co-inhibitory signals.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!