Search results for "IL-2 receptor"

2016

Interleukin-1 (IL-1) plays a crucial role in numerous inflammatory diseases via action on its only known signaling IL-1 receptor type 1 (IL-1R1). To investigate the role of IL-1 signaling in selected cell types, we generated a new mouse strain in which exon 5 of the Il1r1 gene is flanked by loxP sites. Crossing of these mice with CD4-Cre transgenic mice resulted in IL-1R1 loss of function specifically in T cells. These mice, termed IL-1R1ΔT, displayed normal development under steady state conditions. Importantly, isolated CD4 positive T cells retained their capacity to differentiate toward Th1 or Th17 cell lineages in vitro, and strongly proliferated in cultures supplemented with either ant…

Silencing of Foxp3 enhances the antitumor efficacy of GM-CSF genetically modified tumor cell vaccine against B16 melanoma

2017

Antonio Miguel,1 Luis Sendra,1 Verónica Noé,2 Carles J Ciudad,2 Francisco Dasí,3,4 David Hervas,5 María José Herrero,1,6 Salvador F Aliño17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 7Clinical Pharmacology Unit, ACM Hospital Univers…

Peripherally Induced Regulatory T Cells: Recruited Protectors of the Central Nervous System against Autoimmune Neuroinflammation

2017

Defects in regulatory T cells (Treg cells) aggravate multiple sclerosis (MS) after its onset and the absence of Treg cell functions can also exacerbate the course of disease in an animal model of MS. However, autoimmune neuroinflammation in many MS models can be acutely provoked in healthy animals leading to an activation of encephalitogenic T cells despite the normal induction of immune tolerance in the thymus including thymically-produced (t)Treg cells. In contrast, neuroinflammation can be ameliorated or even completely prevented by the antigen-specific Treg cells formed extrathymically in the peripheral immune system (pTreg cells) during tolerogenic responses to relevant neuronal antige…

Interleukin-9 and T helper type 9 cells in rheumatic diseases

2016

Summary Interleukin (IL)-9 is a 28-30 kDa monomeric glycosylated polypeptide belonging to the IL-7/IL-9 family of proteins that bind to a composite receptor consisting of the private receptor IL-9R and the IL-2 receptor, gamma (IL-2RG), a common gamma subunit shared by the receptors of many different cytokines. The IL-9R is expressed widely and IL-9 impacts a number of effector cells, such as effector T cells, B cells, innate lymphoid cells, mast cells, polymorphonuclear cells, epithelial cells and smooth muscle cells, playing an important role in regulating inflammatory immunity. The critical role of IL-9 in promoting cellular and humoral immune responses makes it an important focus of pot…

Research in practice: Regulatory T cells - targets for therapeutic approaches?

2010

• regulatory T cells • tolerance • signal transduction • autoimmunity • allergies • cancer Summary Regulatory T cells (Tregs) are essential for induction and maintenance of immunological tolerance. They contribute to prevention of autoimmunity by control and modulation of immune responses. The prevalence of autoimmune diseases, chronic infections, cancer and allergies has markedly increased in the last decades. In additions the treatment of these disorders is often unsatisfactory so that improvements are needed. This has stimulated intensive research in the biology of Tregs. Recent studies revealed that naturally occurring CD4 + CD25 + Tregs (nTregs) and induced Tregs (iTregs) are critical …

T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice.

2013

Background & Aims Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft after adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled immune-mediated damage. Methods CD8 + T cells were isolated from m…

RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F.

2008

Background and Aims IL-17–producing CD4 + T-helper cells (Th17) contribute to chronic autoimmune inflammation in the brain, and levels of Th17-derived cytokines increase in patients with colitis, suggesting a role in pathogenesis. We analyzed the roles of Th17 cells and the transcription factor retinoic acid receptor-related organ receptor (ROR)γ, which regulates Th17 differentiation, in chronic intestinal inflammation. Methods Using an adoptive transfer model of colitis, we compared the colitogenic potential of wild-type, interleukin-17A (IL-17A)–, IL-17F–, IL-22–, and RORγ-deficient CD4 + CD25 − T cells in RAG1-null mice. Results Adoptive transfer of IL-17A–, IL-17F–, or IL-22–deficient T…

A Critical Regulatory Role of Leucin Zipper Transcription Factor c-Maf in Th1-Mediated Experimental Colitis

2004

Abstract In this study, we investigated the role of c-Maf, a transcription factor known to induce IL-4 production, in inflammatory bowel diseases and experimental colitis. Although Crohn′s disease (CD) is associated with low IL-4 production by T-bet-expressing Th1 cells in the lamina propria, surprisingly a higher expression of c-Maf in these cells was found as compared with control patients. The relevance of this finding was further evaluated in an animal model of CD induced by adoptive transfer of CD4+CD62L+ T cells in RAG-deficient mice. In this Th1-mediated model, an increase of c-Maf-expressing T lymphocytes in the lamina propria over time was observed. Interestingly, adoptive transfer…

IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells

2007

Regulatory T (T(reg)) cells play a key role in the maintenance of the immune system homeostasis. T(reg) cells can be generated in the periphery under control of TGF-beta, a cytokine involved in the negative control of the immune system. However, TGF-beta cooperates with IL-6 in the generation of Th17 cells, a novel class of effector cells involved in numerous inflammatory diseases, including colitis. Therefore, TGF-beta emerges as a mediator of both anti-inflammatory and pro-inflammatory processes, depending on the local cytokine milieu. Here we demonstrate that IL-21, a type-1 cytokine produced by T cells and involved in the pathogenesis of immune-mediated diseases, prevents the TGF-beta-d…

CD4+CD25+ Regulatory T Cells and TGF-Beta in Mucosal Inflammation

2008

Transforming growth factor-beta (TGF-beta) is an anti-inflammatory cytokine which plays a key role in the maintenance of the immune system homeostasis. Indeed the abrogation of the TGF-beta signaling in immune cells leads to autoimmunity and inflammation in several organs including the gut. TGF-beta acts at multiple levels to maintain the immune system in check. However, TGF-beta has been recently shown to play a key role in the peripheral generation and function of CD4+CD25+ regulatory T cells, a subset of suppressive lymphocytes involved in the control of effector T cell activation and proliferation. Consistently abrogation of Tregs maturation as observed in different systems leads to a p…