Search results for "FOXP3"

Type 1 Diabetes and Autoimmune Thyroid Disease—The Genetic Link

2021

Type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) are the most frequent chronic autoimmune diseases worldwide. Several autoimmune endocrine and non-endocrine disorders tend to occur together. T1D and AITD often cluster in individuals and families, seen in the formation of autoimmune polyendocrinopathy (AP). The close relationship between these two diseases is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and DQ8 (DQA1*0301-DQB1*0302), tightly linked with DR3 and DR4, are the major common genetic predisposition. Moreover, functional single nucleotide polymorphisms (or rare variants) of various genes, such as the cytotoxic T-lym…

The immunosuppressive enzyme IL4I1 promotes FoxP3+regulatory T lymphocyte differentiation

2015

Abstract IL4I1 (interleukin-4-induced gene 1) is a phenylalanine oxidase produced mainly by APCs of myeloid origin, and converts phenylalanine (Phe) to phenylpyruvate, hydrogen peroxide, and ammonia. We have previously shown that IL4I1 is highly expressed by tumor-associated macrophages from various human cancers and facilitates immune evasion from the cytotoxic response in a murine tumor model. Indeed, IL4I1 inhibits T-cell proliferation via hydrogen peroxide toxicity on effector/memory T cells. Here, we explored the effect of IL4I1 on naive CD4(+) T-cell differentiation. We show that IL4I1 stimulates the generation of Foxp3(+) regulatory T (Treg) cells in vitro from human and mouse T cell…

Tumor lymphocyte immune response to preoperative radiotherapy in locally advanced rectal cancer: The LYMPHOREC study

2017

IF 7.719; International audience; Introduction: Some studies have suggested that baseline tumor-infiltrating-lymphocytes (TILs), such as CD8+ and FoxP3+ T-cells, may be associated with a better prognosis in colorectal cancer. We sought to investigate modulation of the immune response by preoperative radiotherapy (preopRT) and its impact on survival in locally advanced rectal cancer (LARC). Materials & Methods: We analyzed data for 237 patients with LARC who received RT. Density of TILS (CD8+ and FoxP3+) in intraepithelial (iTILs) and stromal compartments (sTILs) were evaluated from surgery pathological specimens and biopsies performed at baseline. The primary endpoint was to assess the impa…

Heat-Shock Proteins in Autoimmunity

2013

Heat shock proteins (HSPs), also known as “stress proteins,” are among the highly conserved and immunogenic proteins shared among diverse groups of microbial agents and mammals [1]. Heat and other types of stressful stimuli can increase the cellular expression of HSPs. These proteins have been categorized into different families according to their molecular mass, for example, HSP110, HSP90, HSP70, HSP60, HSP40, HSP20-30, and HSP10 [1–3]. For uniformity, guidelines for the nomenclature of various human HSP families have been proposed [4]. Under physiological conditions, the ubiquitously distributed HSPs maintain the integrity and function of other cellular proteins in stressful conditions. H…

IL-2 Expression in Activated Human Memory FOXP3(+) Cells Critically Depends on the Cellular Levels of FOXP3 as Well as of Four Transcription Factors …

2012

The human CD4(+)FOXP3(+) T cell population is heterogeneous and consists of various subpopulations which remain poorly defined. Anergy and suppression are two main functional characteristics of FOXP3(+)Treg cells. We used the anergic behavior of FOXP3(+)Treg cells for a better discrimination and characterization of such subpopulations. We compared IL-2-expressing with IL-2-non-expressing cells within the memory FOXP3(+) T cell population. In contrast to IL-2-non-expressing FOXP3(+) cells, IL-2-expressing FOXP3(+) cells exhibit intermediate characteristics of Treg and Th cells concerning the Treg cell markers CD25, GITR, and Helios. Besides lower levels of FOXP3, they also have higher levels…

Distinct subsets of regulatory T cells during pregnancy: is the imbalance of these subsets involved in the pathogenesis of preeclampsia?

2008

Abstract Regulatory T cells (CD4 + CD25 + FoxP3 + -Treg cells) are important regulators of tolerance induction during pregnancy. We now found that the number of CD4 + CD25 + FoxP3 + -Treg cells decreases during normal course of pregnancy and even more so in women affected by preeclampsia. The functional activity of these CD4 + CD25 + -Treg cells was significantly reduced in comparison to those of healthy pregnants. Further analysis revealed two Treg subsets that differed with regard to the FoxP3 and CD25 expression. The percentage of both, CD4 + CD25 + FoxP3 high+ -Treg and CD4 + CD25 high+ FoxP3 + , was maximal in the first and second trimenon, but declined severely in the third trimenon. …

Peripherally Circulating CD4+ FOXP3+ CXCR3+ T Regulatory Cells Correlate with Renal Allograft Function

2012

Peripheral immunoregulation depends on T regulatory cell trafficking into the allograft to modulate the local alloresponse. Little is known about the relevance of trafficking receptors for Tregs after solid organ transplantation in humans. In this study, expression of the peripheral chemokine receptors CXCR3 and CCR5 on CD4+ FOXP3+ Treg cells was analysed and correlated with allograft function in renal transplant recipients. Flow cytometry analysis of peripheral blood mononuclear cells of 54 renal transplant recipients receiving a calcineurin inhibitor-based immunosuppression was performed for CD4, CD25, FOXP3, CXCR3 and CCR5 within the first 18 months post-transplantation. Correlation anal…

IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1

2007

IL-27 is an IL-12-related cytokine frequently present at sites of inflammation that can promote both anti- and pro-inflammatory immune responses. Here, we have analyzed the mechanisms how IL-27 may drive such divergent immune responses. While IL-27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti-inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL-27 suppressed the development of adaptive, TGF-beta-induced Forkhead box transcription factor p3-positive (Foxp3(+)) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg develo…

2014

TGF- β is a highly pleiotropic cytokine and a well-known suppressor of inflammatory T cells. Dysregulation in TGF- β function is associated with multiple pathological phenomenons including tumor cell growth, fibrosis and autoimmunity. GARP (glycoprotein A repetitions predominant) is an activation maker on human regulatory T cells (Treg) which is known to modulate the bioavailability of TGF- β . To address the cell-independent regulatory capacity of GARP we generated a soluble GARP protein (sGARP). Interestingly, T cells cultured in presence of sGARP showed SMAD2/3 phosphorylation similar to TGF- β treated T cells. In addition, sGARP function was inhibited by blockade of TGF- β -signaling, s…

Desarrollo y efecto antitumoral de vacunas génicas celulares y silenciamiento génico

2015

La presente tesis utiliza las vacunas antitumorales basadas en células modificadas genéticamente como principal estrategia para intentar lograr una respuesta inmune antitumoral eficaz. La vacunación preventiva con células tumorales modificadas genéticamente ha logrado muy buenos resultados en ratones consiguiendo la inhibición del crecimiento tumoral y la supervivencia final de los mismos. Sin embargo, en la clínica la disponibilidad de ciertas células tumorales es muy baja y su transfección es poco reproducible. Por ello, en esta tesis se plantea como uno de los objetivos principales desarrollar y evaluar el efecto antitumoral de vacunas basadas en complejos celulares formados por células …