H2020Индивидуална стипендия2016–2018

NANOBreg · A new therapeutic platform based on nanotechnology to promote T- and B-regulatory networks

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-05-01 → 2018-05-13
Финансиране от ЕС: 158 122 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Наночастици, покрити със специфични молекули, се изследват за активиране на регулаторни Т-клетки при диабет тип 1. Това помага за разбирането на механизмите, чрез които се потиска автоимунният отговор, без да се уврежда общият имунитет на организма.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

A new therapeutic platform based on nanotechnology to promote T- and B-regulatory networks

Autoimmune diseases are caused by an attack of the immune system against self-tissues, resulting in a loss of structural and/or functional integrity of the targeted tissue. There are more than 100 known autoimmune diseases, affecting approximately 100 million people (~75% women) in both Europe and North America. Autoimmune inflammation associated to the disease is normally induced by cognate interactions between antigen presenting cells (APCs) and autoantigen-specific lymphocytes. An ideal therapy for these disorders would be one capable of selectively blunting the autoimmune response (e.g. targeting autoreactive lymphocytes) without impairing the host immunity. Recently, Santamaria and colleagues discovered that systemic delivery of nanoparticles (NPs) coated with Type-1 Diabetes (T1D)-relevant specific molecules (figure 1) triggers the generation and subsequent expansion of memory autoregulatory T cells (TR1), restoring normoglycemia in diabetic animals. This Project aims at dissecting the mechanistic underpinnings of the cellular network that drives the protection to T1D observed by this new therapeutic platform.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

The complexity of autoimmune responses is a barrier to the design of strategies that can selectively purge the immune system of autoreactivity without impairing systemic immunity. Recently, Santamaria et al. have shown that nanoparticles (NPs) coated with type 1 diabetes (T1D)-relevant peptide–MHC (pMHC) complexes can restore normoglycemia in diabetic animals by blunting the diabetogenic autoimmune response without impairing systemic immunity. pMHC class II-NP therapy functions by expanding, in an epitope-specific manner, autoantigen-experienced T-regulatory-1 (TR1) CD4+ T-cells that inhibit the recruitment of other autoantigenic specificities by: (1) suppressing autoantigen-loaded antigen-presenting cells in the pancreatic lymph nodes (PLNs); and (2) promoting the differentiation of B-cells into B-regulatory cells. Importantly, they have shown that human T1D-relevant pMHC class II-NPs also promote human TR1 CD4+ T-cell formation in NSG mice engrafted with peripheral blood mononuclear cells from recent onset T1D patients. Here, I propose a multidisciplinary approach to test the following hypotheses: (1) Breg formation is driven by a cognate interaction between TR1 cells and autoreactive B-cells; (2) TR1-derived cytokines play critical roles in TR1-driven Breg conversion in vivo; and (3) the B-cells that are recruited to the PLNs of pMHC-NP-treated humanized NSG mice are enriched for Breg cells. Furthermore, I will work with the enterprise SEPMAG, to design a scalable magnetic separation device for future clinical development of these compounds.Collectively, NANOBreg will provide new insights into the biology of the TR1-Breg regulatory pathway and will enhance our knowledge on the mechanisms of action of this novel therapeutic approach. In addition, it will address a manufacturing bottleneck by bridging academic research with the manufacturing industry while enhancing my career development in an area of huge potential growth and translational significance.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER · BarcelonaКоординаторИспания