H2020Индивидуална стипендия2019–2022

RoBE · Study of the role of BANK1 in antibody production and antibody-independent functions of B cells in SLE

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

Период: 2019-09-16 → 2022-10-21
Финансиране от ЕС: 259 399 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Ролята на протеина BANK1 при производството на антитела и функциите на B-клетките при системния лупус се анализират за разбиране на това заболяване. По-доброто познаване на тези процеси помага за разработването на по-специфични терапии за пациентите.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Study of the role of BANK1 in antibody production and antibody-independent functions of B cells in SLE

Lupus is a debilitating, inflammatory autoimmune disease most common in women ages 15-45, or during their reproductive years, in a ratio of 9 women to 1 man. This is a condition where the immune system reacts excessively causing inflammation in different organs and resulting in a broad range of clinical manifestations with periods of remission and flares. Patients affected by lupus have a reduced quality of life and productivity, while the care and treatment of lupus represent a social and economic burden for patients and the health care system. Currently, there is no treatment that cures lupus, in fact, treatments are limited to controlling pain and inflammation to reduce disease activity. Lupus is a multifactorial disease where genetic susceptibility combined with environmental factors trigger the autoimmune response. The principal characteristic of the disease is the high levels of antibodies against self-nucleic acid structures produced by B cells, which make the basis of the disease. However, B cells have other functions, such as producing inflammatory and anti-inflammatory mediators, called cytokines, and can also help to activate other immune cells. Recent therapies targeting B cells showed positive results, emphasizing the importance of B cells in the pathogenesis of lupus. Therefore, it is important to further investigate the different functions of B cells and their regulation to develop more specific therapies to treat lupus. It is known that in Europe 1 in 750 women suffer from lupus. These numbers represent a heavy economic and social burden since lupus affects women in their more productive years. Lupus affects every part of a patient´s life, work, school, finances, family, relationships, and mental and emotional well-being. Thus, finding novel and more specific treatments that help to reduce disease progression will reduce the negative impact of lupus in society. Genetic factors have been associated with lupus development. Among them, a genetic variant of the B cell scaffold protein with Ankyrin repeats 1 (BANK1) has been identified as a genetic risk for developing lupus. BANK1 actively participates in the activation of B cells and in the production of autoantibodies in a lupus model. However, it is not known whether BANK1 regulates the production of either other antibodies or cytokines. Our general objective was to investigate the role of BANK1 signaling in the antibody production and antibody-independent functions of B cells in a mouse model of Lupus.

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

Цел на проекта

Systemic Lupus Erythematosus (SLE, Lupus) is a life-threatening and incurable autoimmune disease that affects primarily women, its pathogenesis is related with an exaggerated B cells activation that results both in the generation of antibodies against self-nuclear acid antigens and in the generation of subsets of B cells that can exert antibody-independent roles in Lupus. However, the mechanisms that regulate aberrant B cell functions are poorly understood. In this project, we propose to investigate the role of the B cell scaffold protein with ankyrin repeats 1 (BANK1) in the B cell activation signaling pathways in a mouse model of Lupus. We have previously reported that the absence of BANK1 signaling in mice susceptible to Lupus resulted in the reduction of the activation of B cells, circulating total IgG2c and IgG autoantibodies, pro-inflammatory cytokines, and transcription factors related with TLR7 activation. Our data suggest that BANK1 is an important mediator of B cell hyperactivation. We hypothesize that BANK1 plays an important role in B cell signaling affecting their activation and effector functions in Lupus, however we do not fully understand yet the mechanism behind the function of BANK1. Our specific aims are: 1) to define how BANK1 signaling drives class switch recombination, 2) to determine the mechanism by which BANK1 regulates the cytokine production in B cells, and 3) to examine the participation of BANK1 signaling in the differentiation of pathogenic B cell subsets. To accomplish our objectives, we will use flow and mass cytometry, RNA-based next-generation sequencing (RNA-seq) analysis, the assay for transposase-accessible chromatin followed by deep sequencing (ATAC-seq), and a chromatin immunoprecipitation (ChIP) assay. We expect that the results of these studies will help to understand the molecular mechanism underlying the pathogenic B cell response in Lupus and will lead to identification of new avenues for therapeutic development.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUD M.P. · SevillaКоординаторИспания