Utforska autoreaktiva B-celler och deras redoxreglering: Insikter i Autoimmuna sjukdomar.

Mike Aoun, Karolinska Institutet, 75000

Bakgrund och motivering

Autoimmune diseases, including rheumatoid arthritis (RA), pose a substantial health burden, yet effective treatments remain elusive. Autoreactive B cells have been traditionally viewed as pathogenic, but recent findings reveal a suppressive subset, offering new therapeutic avenues. This research addresses the critical need for a deeper understanding of autoreactive B cells to develop novel treatments, potentially transforming the lives of individuals grappling with autoimmune disorders, particularly RA.

Syfte och mål

AIM 1: Molecular Insights for Early RA Diagnosis

Our primary goal is to scrutinize autoreactive B cells in both RA patients and healthy counterparts. Through this analysis, we aim to uncover markers that can serve as early diagnostic indicators or even predictive measure and potential therapeutic focal points.

AIM 2: Unraveling Ncf1's Influence Over Autoreactive B cells

We delve into the regulatory mechanisms governed by Ncf1 in autoreactive B cells and cognate T cells, extending the scope of our findings beyond RA to encompass diverse autoimmune conditions.

Metod

AIM 1:

We will sort autoreactive B cells from age/sex matched healthy and RA donors, utilizing SmartSeq3 RNA sequencing for comprehensive transcriptomic analysis. Differential gene expression will be analyzed, and B cell receptor clonal expansion will be examined. Collaborating with NBIS and Scilifelab ensures robust bioinformatics support.

AIM 2:

We will utilize a unique conditional Ncf1 knockout mouse strain specific to B cells to investigate Ncf1's role in autoimmune diseases. Through mechanistic examinations, we will assess how Ncf1 influences ROS production, autoreactive B cell activation, T cell proliferation, and suppression functions, shedding light on its regulatory mechanisms within autoimmune contexts.

Betydelse för patienten

This research program promises substantial clinical and scientific value. In the short term, it may lead to early diagnosis and personalized treatments for RA, alleviating pain and enhancing patients' lives. Over the long term, it has the potential to revolutionize autoimmune disease management, offering more effective, targeted therapies that can halt disease progression and improve the prognosis and quality of life for a wide range of patients. Ultimately, our research aims to significantly improve the long-term prognosis and quality of life for individuals burdened by autoimmune diseases.