Shared lung and joint T cell repertoire in early rheumatoid arthritis driven by cigarette smoking

医学 类风湿性关节炎 免疫学 类风湿结节 吸烟 剧目 内科学 声学 物理
作者
Koen Venken,Matthias Jarlborg,Frederik Stevenaert,Thomas Malfait,Carolien Vlieghe,Yann Abraham,Teddy Manuello,Tine Decruy,Stijn Vanhee,Hans Wils,Pieter J. Peeters,Philippe Carron,Filip Van den Bosch,Viggo Van Tendeloo,Bart N. Lambrecht,Ruth Wittoek,Peggy Jacques,Dirk Elewaut
出处
期刊:Annals of the Rheumatic Diseases [BMJ]
卷期号:: ard-226284
标识
DOI:10.1136/ard-2024-226284
摘要

Objectives Smoking has been associated with an increased risk of developing rheumatoid arthritis (RA) in individuals carrying shared epitope (SE) HLA-DRB1 alleles. Yet, little is known about the regional and systemic T cell dynamics of smoking and a potential link to T cell infiltration in inflamed synovia. In this study, we, therefore, sought to study T cell features in lung and inflamed joints in smoking versus non-smoking patients. Methods We set up a framework to monitor T cells in paired bronchoalveolar lavage fluid, blood and inflamed synovium tissue samples from 17 new-onset treatment naïve anticitrullinated protein antibody+RA patients. T cell receptor (TCR) repertoire of index-sorted tissue residing in T cells was determined by single-cell TCR sequencing coupled with deep immunophenotyping. Results A significant enrichment of CD4+ and CD8+ T cells was seen in synovial samples from smoking versus non-smoking patients, along with an increase in expanded T cell clonotypes. This was particularly pronounced among SE+smokers, suggestive of a synergic gene-smoke effect. Strikingly, identical TCR clonalities were present in matched lung and joint samples of RA smokers, the majority being also detectable in circulation. This was mirrored by an increased clustering of lung and synovium TCRs across patients, suggesting a shared specificity by conserved motifs. The lung-joint shared T cell clonotypes showed a restricted TCR gene usage and exhibited a particular 4-1BB+CD57 hi effector profile within the inflamed synovium. Conclusion The data indicate a profound interplay between a strong MHC predisposition, smoking and induction of autoimmunity by shaping the TCR repertoire.

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