Exhaustion profile on classical monocytes after LPS stimulation on Crohn’s disease patients

IF 2.2 4区 医学 Q3 IMMUNOLOGY Human Immunology Pub Date : 2025-03-01 Epub Date: 2025-02-13 DOI:10.1016/j.humimm.2025.111257
Lucas Pires Garcia Oliveira , Rafaela Gomes Xavier , Claudia Concer Viero Nora , Cristóvão Luis Pitangueira Mangueira , Eliane Aparecida Rosseto , Thiago Aloia , Jaime Zaladek Gil , Arceu Scanavini Neto , Filipa Blasco Tavares Pereira Lopes , Karina Inacio Carvalho
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Abstract

Crohn’s disease is a type of inflammatory bowel disease that leads to symptoms such as diarrhea, abdominal pain, weight loss, and increased risk of developing tumors. The immune system plays a vital role in the gastrointestinal tract by maintaining tolerance to commensal antigens and food. However, in Crohn’s disease, this tolerance mechanism is disrupted, resulting in chronic inflammatory responses. The involvement of the immune system is central to Crohn’s disease, with a wide range of immune cells including monocytes, being affected. Due to the limited understanding of the role of monocytes in Crohn’s disease, our study aimed to clarify the cytokine production and activation profile of monocytes subsets in the context of this condition.
We used multiparametric flow cytometry to analyze the status of monocyte, quantified gene expression using qPCR, and created a correlation matrix to connect the flow cytometry data with the qPCR results through a bioinformatics approach. Our findings indicate that patients with Crohn’s disease show a reduction in all monocyte subsets. Additionally, classical monocytes exhibit an exhaustion profile characterized by increased CD38 expression and reduced IL-1β production following LPS stimulation in patient groups. These results suggest that monocyte subsets play distinct roles in the disease’s pathophysiology of Crohn’s disease, potentially contributing to chronic inflammation and impairing the resolution of the immune response.
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克罗恩病患者LPS刺激后经典单核细胞的衰竭特征
克罗恩病是一种炎症性肠病,会导致腹泻、腹痛、体重减轻和患肿瘤的风险增加等症状。免疫系统通过维持对共生抗原和食物的耐受性在胃肠道中起着至关重要的作用。然而,在克罗恩病中,这种耐受机制被破坏,导致慢性炎症反应。免疫系统的参与是克罗恩病的核心,包括单核细胞在内的多种免疫细胞受到影响。由于对单核细胞在克罗恩病中的作用的了解有限,我们的研究旨在阐明在这种情况下单核细胞亚群的细胞因子产生和激活谱。我们使用多参数流式细胞术分析单核细胞状态,使用qPCR定量基因表达,并通过生物信息学方法建立关联矩阵将流式细胞术数据与qPCR结果联系起来。我们的研究结果表明,克罗恩病患者显示所有单核细胞亚群的减少。此外,经典单核细胞表现出衰竭特征,其特征是在LPS刺激后CD38表达增加和IL-1β产生减少。这些结果表明,单核细胞亚群在克罗恩病的病理生理中发挥着独特的作用,可能导致慢性炎症和损害免疫反应的解决。
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来源期刊
Human Immunology
Human Immunology 医学-免疫学
CiteScore
5.40
自引率
7.40%
发文量
107
审稿时长
12 days
期刊介绍: The journal''s scope includes understanding the genetic and functional mechanisms that distinguish human individuals in their immune responses to allografts, pregnancy, infections or vaccines as well as the immune responses that lead to autoimmunity, allergy or drug hypersensitivity. It also includes examining the distribution of the genes controlling these responses in populations. Research areas include: Studies of the genetics, genomics, polymorphism, evolution, and population distribution of immune-related genes Studies of the expression, structure and function of the products of immune-related genes Immunogenetics of susceptibility to infectious and autoimmune disease, and allergy The role of the immune-related genes in hematopoietic stem cell, solid organ, and vascularized composite allograft transplant Histocompatibility studies including alloantibodies, epitope definition, and T cell alloreactivity Studies of immunologic tolerance and pregnancy T cell, B cell, NK and regulatory cell functions, particularly related to subjects within the journal''s scope Pharmacogenomics and vaccine development in the context of immune-related genes Human Immunology considers immune-related genes to include those encoding classical and non-classical HLA, KIR, MIC, minor histocompatibility antigens (mHAg), immunoglobulins, TCR, BCR, proteins involved in antigen processing and presentation, complement, Fc receptors, chemokines and cytokines. Other immune-related genes may be considered. Human Immunology is also interested in bioinformatics of immune-related genes and organizational topics impacting laboratory processes, organ allocation, clinical strategies, and registries related to autoimmunity and transplantation.
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