Search results for "Humanized mouse"

2015

Regulatory T cells (Treg) control immune cell function as well as non-immunological processes. Their far-reaching regulatory activities suggest their functional manipulation as a means to sustainably and causally intervene with the course of diseases. Preclinical tools and strategies are however needed to further test and develop interventional strategies outside the human body. "Humanized" mouse models consisting of mice engrafted with human immune cells and tissues provide new tools to analyze human Treg ontogeny, immunobiology, and therapy. Here, we summarize the current state of humanized mouse models as a means to study human Treg function at the molecular level and to design strategie…

Abstract 4082: Preclinical assessment of external or targeted radiotherapy in combination with immunotherapies and co-development of companion imagin…

2019

Abstract Immunotherapies have proven to be highly efficient for cancer treatments and combination with either internal vectorized or external radiotherapies can enhance this efficacy through notably increasing tumor immune infiltrate. The clinical evaluation of such combination therapies requires expertise and exquisite processes in multiple fields, immunotherapy, radiotherapy and nuclear medicine. Similarly, this applies into preclinical settings for assessing proof of concept of novel combinations. Herein, we will present our preclinical evaluation process to combine external or internal (i.e. lutetium-177 radiolabeled molecule) radiotherapy with immunotherapies that include radiochemistr…

2021

The presence and interaction of immune cells in the tumor microenvironment is of significant importance and has a great impact on disease progression and response to therapy. Hence, their identification is of high interest for prognosis and treatment decisions. Besides detailed phenotypic analyses of immune, as well as tumor cells, spatial analyses is an important parameter in the complex interplay of neoplastic and immune cells—especially when moving into focus efforts to develop and validate new therapeutic strategies. Ex vivo analysis of tumor samples by immunohistochemistry staining methods conserves spatial information is restricted to single markers, while flow cytometry (disrupting t…

Reduction Of Pulmonary Inflammation Through HIV-1 Envelope Protein GP120 In A Humanized Mouse Model Of Allergic Asthma Depends On Regulatory T Cells

2011

Analysis Of Pulmonary Inflammation Using Humanized Mouse Models

2010

Repression of Cyclic Adenosine Monophosphate Upregulation Disarms and Expands Human Regulatory T Cells

2011

Abstract The main molecular mechanism of human regulatory T cell (Treg)-mediated suppression has not been elucidated. We show in this study that cAMP represents a key regulator of human Treg function. Repression of cAMP production by inhibition of adenylate cyclase activity or augmentation of cAMP degradation through ectopic expression of a cAMP-degrading phosphodiesterase greatly reduces the suppressive activity of human Treg in vitro and in a humanized mouse model in vivo. Notably, cAMP repression additionally abrogates the anergic state of human Treg, accompanied by nuclear translocation of NFATc1 and induction of its short isoform NFATc1/αA. Treg expanded under cAMP repression, however,…

The LDL receptor in the retina: the missing link in aging, the new target in dietary prevention

2012

National audience; Purpose: The discovery of the LDL receptor (LDLR) in 1985 by Brown and Goldstein was awarded by a Nobel Prize. The LDLR has initially been identified for its role in mediating the endocytosis of LDL particles in the vascular endothelium. The deposition of lipids, including cholesterol and cholesteryl esters in Bruch’s Membrane in the one hand, and in the vessel intima in the other hand, is one of the common features of age related macular degeneration (AMD) and cardiovascular disease (CVD). Dietary habits with high intakes of omega 3 long chain fatty acids (LCFA) have been associated with AMD prevention. Similar effects have been demonstrated in CVD prevention. The mechan…

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…