Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Erlangen, Germany.
Front Immunol. 2022 Jul 8;13:908174. doi: 10.3389/fimmu.2022.908174. eCollection 2022.
Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular events driven by abnormal platelet clotting effects. Platelets are produced by megakaryocytes, deriving from megakaryocyte erythrocyte progenitors (MEP) in the bone marrow. Increased megakaryocyte expansion across common autoimmune diseases was shown for RA, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). In this context, we evaluated the role of the microbial-derived short chain fatty acid (SCFA) propionate on hematopoietic progenitors in the collagen induced inflammatory arthritis model (CIA) as we recently showed attenuating effects of preventive propionate treatment on CIA severity. , propionate treatment starting 21 days post immunization (dpi) reduced the frequency of MEPs in the bone marrow of CIA and naïve mice. Megakaryocytes numbers were reduced but increased the expression of the maturation marker CD61. Consistent with this, functional analysis of platelets showed an upregulated reactivity state following propionate-treatment. This was confirmed by elevated histone 3 acetylation and propionylation as well as by RNAseq analysis in Meg-01 cells. Taken together, we identified a novel nutritional axis that skews platelet formation and function.
类风湿关节炎（RA）与心血管事件风险增加有关，其驱动因素是血小板凝结作用异常。血小板由巨核细胞产生，而巨核细胞来源于骨髓中的巨核细胞红细胞前体（MEP）。已有研究表明，RA、系统性红斑狼疮（SLE）和原发性干燥综合征（pSS）等常见自身免疫性疾病存在巨核细胞过度扩张现象。在此背景下，我们评估了微生物衍生的短链脂肪酸（SCFA）丙酸盐对胶原诱导性炎症关节炎模型（CIA）中造血祖细胞的作用，因为我们最近发现预防性丙酸盐治疗可减轻 CIA 严重程度。结果表明，从免疫后 21 天（dpi）开始进行丙酸盐治疗可减少 CIA 和正常小鼠骨髓中 MEP 的频率。巨核细胞数量减少，但成熟标志物 CD61 的表达增加。与此一致，丙酸盐处理后的血小板功能分析显示反应性状态上调。这一结果通过 Meg-01 细胞中的组蛋白 3 乙酰化和丙酰化以及 RNAseq 分析得到了证实。综上所述，我们确定了一条新的营养轴，该轴可影响血小板的形成和功能。
