Self-reactive B cells in the GALT are actively curtailed to prevent gut inflammation

Shukla, Ashima; Chen, Cindi; Jellusova, Julia; Leung, Charlotte R; Kao, Elaine; Bhat, Numana; Lin, Wai Wai; Apgar, John R.; Rickert, Robert C.

doi:10.1172/jci.insight.130621

Cited by 6 publications

(5 citation statements)

References 46 publications

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“…PB/PC refers to two types of cells: plasmablasts (precursors of plasma cells) and plasma cells, and PB/PC%B cells represent the percentage of B cells in peripheral blood and spleen. Under normal circumstances, the ratio of PB/PC to lymphocytes in peripheral blood remains at a relatively high level, which is crucial for antibody production and immune cell clearance ( 26 ). Fluctuations in PB/PC%B cells often impact immune regulation and the intensity of immune responses ( 27 ), for instance, clinically predicting an increased risk of developing multiple sclerosis due to excessive immune reactions when the baseline PB/PC percentage falls below 0.1% ( 28 ), another study on anxiety comorbidity in adolescents showed a significant increase in lymphocyte ratios, suggesting a potential link between anxiety disorders and inflammatory responses ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study

Ma,

Zhao,

Zhao

et al. 2024

Front. Immunol.

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BackgroundGeneralized anxiety disorder (GAD) is a prevalent emotional disorder that has received relatively little attention regarding its immunological basis. Recent years have seen the widespread use of high-density genetic markers such as SNPs or CNVs for genotyping, as well as the advancement of genome-wide association studies (GWAS) technologies, which have facilitated the understanding of immunological mechanisms underlying several major psychiatric disorders. Despite these advancements, the immunological basis of GAD remains poorly understood. In light of this, we aimed to explore the causal relationship between immune cells and the disease through a Mendelian randomization study.MethodsThe summary information for GAD (Ncase=4,666, Ncontrol=337,577) was obtained from the FinnGen dataset. Summary statistics for the characterization of 731 immune cells, including morphological parameters (MP=32), median fluorescence intensity (MFI=389), absolute cells (AC=118), and relative cells (RC=192), were derived from the GWAS catalog. The study involved both forward MR analysis, with immune cell traits as the exposure and GAD as the outcome, and reverse MR analysis, with GAD as the exposure and immune cell traits as the outcome. We performed extensive sensitivity analyses to confirm the robustness, heterogeneity, and potential multi-biological effects of the study results. Also, to control for false positive results during multiple hypothesis testing, we adopted a false discovery rate (FDR) to control for statistical bias due to multiple comparisons.ResultsAfter FDR correction, GAD had no statistically significant effect on immunophenotypes. Several phenotypes with unadjusted low P-values are worth mentioning, including decreased PB/PC levels on B cells(β=-0.289, 95%CI=0.044~0.194, P=0.002), reduced PB/PC AC in GAD patients (β=-0.270, 95% CI=0.77~0.92, P=0.000), and diminished PB/PC on lymphocytes (β=-0.315, 95% CI=0.77~0.93, P=0.001). GAD also exerted a causal effect on CD27 on IgD-CD38br (β=-0.155,95%CI=0.78~0.94,P=0.002), CD20-%B cell (β= -0.105,95% CI=0.77~0.94, P=0.002), IgD-CD38br%lymphocyte(β=-0.305, 95%CI=0.79~0.95, P=0.002), FSC-A level on granulocytes (β=0.200, 95%CI=0.75~0.91, P=8.35×10−5), and CD4RA on TD CD4+(β=-0.150, 95% CI=0.82~1.02, P=0.099). Furthermore, Two lymphocyte subsets were identified to be significantly associated with GAD risk: CD24+ CD27+ B cell (OR=1.066,95%CI=1.04~1.10,P=1.237×10−5),CD28+CD4+T cell (OR=0.927, 95%CI=0.89~0.96, P=8.085×10−5).ConclusionThe study has shown the close association between immune cells and GAD through genetic methods, thereby offering direction for future clinical research.

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Section: Discussionmentioning

confidence: 99%

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study

Ma,

Zhao,

Zhao

et al. 2024

Front. Immunol.

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“…[ 69 ] B cells can also be present both in the GALT and in the FAE, [ 70 ] and intervene in the immune response by producing immunoglobulins and immune‐modulatory cytokines, such as IL‐10. [ 71 ] Natural killer (NK) cells are also present in the GALT and are involved in mucosal innate immunity due to their cytolytic activity. [ 72 ]…”

Section: Cellular Biology Of the Gutmentioning

confidence: 99%

Recent Advances in Cell‐Based In Vitro Models to Recreate Human Intestinal Inflammation

Macedo,

Dias Neto,

Pastrana

et al. 2023

Advanced Science

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Inflammatory bowel disease causes a major burden to patients and healthcare systems, raising the need to develop effective therapies. Technological advances in cell culture, allied with ethical issues, have propelled in vitro models as essential tools to study disease aetiology, its progression, and possible therapies. Several cell‐based in vitro models of intestinal inflammation have been used, varying in their complexity and methodology to induce inflammation. Immortalized cell lines are extensively used due to their long‐term survival, in contrast to primary cultures that are short‐lived but patient‐specific. Recently, organoids and organ‐chips have demonstrated great potential by being physiologically more relevant. This review aims to shed light on the intricate nature of intestinal inflammation and cover recent works that report cell‐based in vitro models of human intestinal inflammation, encompassing diverse approaches and outcomes.

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“…The adaptive immune system refers to gut-associated lymphoid tissue (GALT) and SIgA, which is one of the important components of the immune system (29). GALT mainly consists of multi-follicular lymphoid tissues, such as Peyer's lymph nodes riched in lymph follicles, mesenteric lymph nodes (MLNs), isolated lymphoid follicles (ILF), and scattered lymphocytes in the lamina propria and epithelium of the mucosa (30)(31)(32). As the largest lymphoid tissue in the body, GALT recognizes foreign antigens and abnormal antigens in time by ingesting, processing, and presenting antigens.…”

Section: Intestinal Immune Barriermentioning

confidence: 99%

“…And after specifically recognizing foreign antigens, GALT promotes the production of cytokines and antibodies to coordinate with the immune response. Besides, it also activates T and B lymphocytes to establish effective adaptive immune response and induce the mucosal immune response or immune tolerance (31,32). Another component of the adaptive immune system in the intestinal immune barrier is SIgA, which is the most abundant immunoglobulin in the body released by B cells (33).…”

Section: Intestinal Immune Barriermentioning

confidence: 99%

The Role of Intestinal Mucosal Barrier in Autoimmune Disease: A Potential Target

Liu

Wang

et al. 2022

Front. Immunol.

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Autoimmune diseases are a series of diseases involving multiple tissues and organs, characterized by the over production of abnormal multiple antibodies. Although most studies support that the impaired immune balance participates in the development of autoimmune diseases, the specific pathogenesis of it is not fully understood. Intestinal immunity, especially the intestinal mucosal barrier has become a research hotspot, which is considered to be an upstream mechanism leading to the impaired immune balance. As an important defense barrier, the intestinal mucosal barrier regulates and maintains the homeostasis of internal environment. Once the intestinal barrier function is impaired under the effect of multiple factors, it will destroy the immune homeostasis, trigger inflammatory response, and participate in the development of autoimmune diseases in the final. However, the mechanism of the intestinal mucosal barrier how to regulate the homeostasis and inflammation is not clear. Some studies suggest that it maintains the balance of immune homeostasis through the zonulin pathway, intestinal microbiome, and Toll-like receptor signaling pathway. Our review focused on the composition and the function of the intestinal mucosal barrier to describe the research progress of it in regulating the immune homeostasis and inflammation, and also pointed that the intestinal mucosal barrier was the potential targets in the treatment of autoimmune diseases.

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Self-reactive B cells in the GALT are actively curtailed to prevent gut inflammation

Cited by 6 publications

References 46 publications

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study

Recent Advances in Cell‐Based In Vitro Models to Recreate Human Intestinal Inflammation

The Role of Intestinal Mucosal Barrier in Autoimmune Disease: A Potential Target

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