scholarly journals Gut dysbiosis is associated with acceleration of lupus nephritis

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Giancarlo R. Valiente ◽  
Armin Munir ◽  
Marcia L. Hart ◽  
Perry Blough ◽  
Takuma T. Wada ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Th17 Cells ◽  
Kidney Tissue ◽  
Tissue Expression ◽  
Lymphoid Cells ◽  
Intestinal Microbiome ◽  
Host Immune System ◽  
Inflammatory Conditions ◽  
Gut Colonization ◽  
Complex Deposition

AbstractThe gut microbiota (GM) exerts a strong influence over the host immune system and dysbiosis of this microbial community can affect the clinical phenotype in chronic inflammatory conditions. To explore the role of the GM in lupus nephritis, we colonized NZM2410 mice with Segmented Filamentous Bacteria (SFB). Gut colonization with SFB was associated with worsening glomerulonephritis, glomerular and tubular immune complex deposition and interstitial inflammation compared to NZM2410 mice free of SFB. With SFB colonization mice experienced an increase in small intestinal lamina propria Th17 cells and group 3 innate lymphoid cells (ILC3s). However, although serum IL-17A expression was elevated in these mice, Th17 cells and ILC3s were not detected in the inflammatory infiltrate in the kidney. In contrast, serum and kidney tissue expression of the macrophage chemoattractants MCP-1 and CXCL1 were significantly elevated in SFB colonized mice. Furthermore, kidney infiltrating F4/80+CD206+M2-like macrophages were significantly increased in these mice. Evidence of increased gut permeability or “leakiness” was also detected in SFB colonized mice. Finally, the intestinal microbiome of SFB colonized mice at 15 and 30 weeks of age exhibited dysbiosis when compared to uncolonized mice at the same time points. Both microbial relative abundance as well as biodiversity of colonized mice was found to be altered. Collectively, SFB gut colonization in the NZM2410 mouse exacerbates kidney disease, promotes kidney M2-like macrophage infiltration and overall intestinal microbiota dysbiosis.

scholarly journals Gut Dysbiosis with a Pathobiont Shifts the Intestinal Microbiota Profile and Accelerates Lupus Nephritis

2020 ◽  
Author(s):  
Giancarlo R. Valiente ◽  
Armin Munir ◽  
Marcia L. Hart ◽  
Perry Blough ◽  
Takuma T. Wada ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Intestinal Microbiota ◽  
Th17 Cells ◽  
Kidney Tissue ◽  
Tissue Expression ◽  
Lymphoid Cells ◽  
Intestinal Microbiome ◽  
Host Immune System ◽  
Inflammatory Conditions ◽  
Gut Colonization

ABSTRACTThe gut microbiota (GM) exerts a strong influence over the host immune system and dysbiosis of this microbial community can affect the clinical phenotype in chronic inflammatory conditions. To explore the role of the GM in lupus nephritis, we colonized NZM2410 mice with Segmented Filamentous Bacteria (SFB). Gut colonization with SFB was associated with worsening glomerulonephritis, glomerular and tubular immune complex deposition and interstitial inflammation compared to NZM2410 mice free of SFB. With SFB colonization mice experienced an increase in small intestinal lamina propria Th17 cells and group 3 innate lymphoid cells (ILC3s). However, although serum IL-17A expression was elevated in these mice, Th17 cells and ILC3s were not detected in the inflammatory infiltrate in the kidney. In contrast, serum and kidney tissue expression of the macrophage chemoattractants MCP-1 and CXCL1 were significantly elevated in SFB colonized mice. Furthermore, kidney infiltrating F4/80+CD206+ M2-like macrophages were significantly increased in these mice. Evidence of increased gut permeability or “leakiness” was detected in SFB colonized mice. Finally, the intestinal microbiome of SFB colonized mice at 15 and 30 weeks of age exhibited dysbiosis when compared to uncolonized mice at the same time points. Both microbial relative abundance as well as biodiversity of colonized mice was found to be altered. Collectively, SFB gut colonization in the NZM2410 mouse exacerbates kidney disease, promotes kidney M2-like macrophage infiltration and overall intestinal microbiota dysbiosis.

scholarly journals Early microbial contact, the breast milk microbiome and child health

2015 ◽  
Vol 7 (1) ◽  
pp. 5-14 ◽  
Author(s):  
S. Rautava
Keyword(s):  
Breast Milk ◽  
Early Life ◽  
Mode Of Delivery ◽  
Therapeutic Interventions ◽  
Intestinal Microbiome ◽  
Amniotic Cavity ◽  
Cesarean Section Delivery ◽  
Inflammatory Conditions ◽  
Gut Colonization ◽  
The Impact

The significance of contact with microbes in early life for subsequent health has been the subject of intense research during the last 2 decades. Disturbances in the establishment of the indigenous intestinal microbiome caused by cesarean section delivery or antibiotic exposure in early life have been linked to the risk of immune-mediated and inflammatory conditions such as atopic disorders, inflammatory bowel disease and obesity later in life. Distinct microbial populations have recently been discovered at maternal sites including the amniotic cavity and breast milk, as well as meconium, which have previously been thought to be sterile. Our understanding of the impact of fetal microbial contact on health outcomes is still rudimentary. Breast milk is known to modulate immune and metabolic programming. The breast milk microbiome is hypothesized to guide infant gut colonization and is affected by maternal health status and mode of delivery. Immunomodulatory factors in breast milk interact with the maternal and infant gut microbiome and may mediate some of the health benefits associated with breastfeeding. The intimate connection between the mother and the fetus or the infant is a potential target for microbial therapeutic interventions aiming to support healthy microbial contact and protect against disease.

scholarly journals Antigen presentation by type 3 innate lymphoid cells instructs the differentiation of gut microbiota-specific regulatory T cells

2021 ◽  
Author(s):  
Ranit Kedmi ◽  
Tariq Najar ◽  
Kailin R. Mesa ◽  
Allyssa Grayson ◽  
Lina Kroehling ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Differentiation ◽  
Antigen Presentation ◽  
Th17 Cells ◽  
Immune Cell ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Host Immune System ◽  
Type 3

The mutualistic relationship of gut-resident microbiota and cells of the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a poised, but largely non-aggressive, immune cell compartment1,2. Consequences of disturbing this balance, by environmental or genetic factors, include proximal inflammatory conditions, like Crohn's disease, and systemic illnesses, both metabolic and autoimmune. One of the means by which this equilibrium is achieved is through induction of both effector and suppressor or regulatory arms of the adaptive immune system. In mice, Helicobacter species induce regulatory (iTreg) and follicular helper (Tfh) T cells in the colon-draining mesenteric lymph nodes under homeostatic conditions, but can instead induce inflammatory Th17 cells and colitis when iTreg cells are compromised3,4. How Helicobacter hepaticus and other gut bacteria direct T cells to adopt distinct functions remains poorly understood. Here, we investigated which cells and molecular components are required to convey the microbial instruction for the iTreg differentiation program. We found that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells, was both required and sufficient for iTreg induction. These RORγt+ cells, likely to be type 3 innate lymphoid cells (ILC3), require the MHC class II antigen presentation machinery, the chemokine receptor CCR7, and αv integrin, which activates TGF-β, for iTreg cell differentiation. In the absence of any of these, instead of iTreg cells there was expansion of microbiota-specific pathogenic Th17 cells, which were induced by other antigen presenting cells (APCs) that did not require CCR7. Thus, intestinal commensal microbes and their products target multiple APCs with pre-determined features suited to directing appropriate T cell differentiation programs, rather than a common APC that they endow with appropriate functions. Our results illustrate the ability of microbiota to exploit specialized functions of distinct innate immune system cells, targeting them to achieve the desired composition of equipoised T cells, thus maintaining tolerance.

Correlation Between Serological Makers and Immunofluorescence Deposits i n Kidney Tissue of Patients with Lupus Nephritis

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Haider S Al-Hadad ◽  
Aqeel Abbas Matrood ◽  
Maha Abdalrasool Almukhtar ◽  
Haider Jabur Kehiosh ◽  
Riyadh Muhi Al-Saegh
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Biopsy ◽  
Pearson Correlation ◽  
Standard Procedure ◽  
Kidney Tissue ◽  
P Value ◽  
American College Of Rheumatology ◽  
Immune Deposits ◽  
Number Of Patients

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease. Few biomarkers for SLE have been validated and widely accepted for the laboratory follow-up of inflammatory activity. In SLE patients, with lupus nephritis (LN), complement activation leads to fluctuation of serum C3 and C4 that are frequently used as clinicalm biomarker of disease activity in SLE. Patients and Methods: In this study the number of patients were 37, seven patients were excluded for incomplete data collection, 28 were females ,2 were males. The duration of the study is two years from 2015 to 2017. Patients were considered to have SLE and LN according to American College of Rheumatology (ACR) criteria, and International Society of Nephrology/ Renal Pathology Society (ISN/RPS). All patients were evaluated withm clinical presentation, laboratory investigations. Our patients underwent kidney biopsy according to standard procedure by Kerstin Amann, and their tissue specimens were studied in the laboratory with light microscope (LM) and immunofluorescence microscope reagents. The relationship between the serological markers and immunofluorescence deposits in kidney biopsy of all patients were studied using the statistical analysis of Pearson correlation and single table student's T test. A P value 0.05 was considered statistically significant. Results: The granular pattern of IF deposits was present in all LN patients, and in more than two third of patients these IF deposits presented in glomerular, tubular, and mesangium sites. While less than one third of patients had IF deposits in the mesangium only. There was no statistically significant correlation between serum ANA, anti-dsDNA, and IF deposits of different types. There was significant correlation between serum C3 and C4 hypocomplementemia and IgG immune deposits in kidney biopsy, and there was significant relationship between serum C3 hypocomplementemia and full house immunofluorescence (FHIF) deposits inm kidney biopsy.Conclusions:Immunofluorescence deposits is mainly granular pattern in LN patients. There was no significant association between serum ANA, anti-dsDNA, and immune deposits in kidney tissue. Immunofluorescence deposits of IgG type correlates significantly with serum C3 and C4 hypocomplemetemia, and these immune deposits in association with low complement levels correlates with LN flare. There was significant correlation between C3 hypocomplementemia and FHIF.

A Comparative Study on the Incidence, Aggravation, and Remission of Lupus Nephritis Based on iTRAQ Technology

2020 ◽  
Vol 23 (7) ◽  
pp. 649-657
Author(s):  
Dong-Jiang Liao ◽  
Xi-Ping Cheng ◽  
Nan Li ◽  
Kang-Li Liang ◽  
Hui Fan ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Tissue ◽  
Quantitative Information ◽  
Enzyme Linked Immunosorbent Assay ◽  
Absolute Quantitation ◽  
Western Blot Method ◽  
Close Relationship ◽  
Polymerase Chain ◽  
Isobaric Tags

Aim and Objective: Lupus nephritis (LN) is one of the major complications of systemic lupus erythematosus (SLE). The specific mechanisms of pathogenesis, aggravation, and remission processes in LN have not been clarified but is of great need in the clinic. Using isobaric tags for relative and absolute quantitation (iTRAQ) technology to screen the functional proteins of LN in mice. Especially under intervention factors of lipopolysaccharide (LPS) and dexamethasone. Methods: Mrl-lps mice were intervened with LPS, dexamethasone, and normal saline (NS) using intraperitoneal injection, and c57 mice intervened with NS as control. The anti-ANA antibody enzyme-linked immunosorbent assay (ELISA) was used to verify disease severity. Kidney tissue is collected and processed for iTRAQ to screen out functional proteins closely related to the onset and development of LN. Western blot method and rt-PCR (real-time Polymerase Chain Reaction) were used for verification. Results: We identified 136 proteins that marked quantitative information. Among them, Hp, Igkv8-27, Itgb2, Got2, and Pcx proteins showed significant abnormal manifestations. Conclusion: Using iTRAQ methods, the functional proteins Hp, Igkv8-27, Itgb2, Got2, and Pcx were screened out for a close relationship with the pathogenesis and development of LN, which is worth further study.

scholarly journals Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation

2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Airway Diseases ◽  
Type 2 Cytokines ◽  
Lymphoid Organogenesis ◽  
Deficient Mice

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.

YAP1 Overexpression Is Associated with Kidney Dysfunction in Lupus Nephritis

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ying Xie ◽  
Yuanyuan Ruan ◽  
Huimei Zou ◽  
Yixin Wang ◽  
Xin Wu ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Tissue ◽  
Mouse Kidney ◽  
Experimental Comparison ◽  
Control Group ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Protein Levels

<b><i>Objective:</i></b> The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. <b><i>Methods:</i></b> C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. <b><i>Results:</i></b> Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. <b><i>Conclusion:</i></b> YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.

scholarly journals Localization and site-specific cell–cell interactions of group 2 innate lymphoid cells

2021 ◽  
Author(s):  
Kiniwa Tsuyoshi ◽  
Kazuyo Moro
Keyword(s):  
Lipid Production ◽  
Allergic Diseases ◽  
Innate Lymphoid Cells ◽  
The Body ◽  
Cell Interactions ◽  
Lymphoid Cells ◽  
Specific Cell ◽  
Inflammatory Conditions ◽  
Group 2 ◽  
Cell Cell

Abstract Group 2 innate lymphoid cells (ILC2s) are novel lymphocytes discovered in 2010. Unlike T or B cells, ILC2s are activated nonspecifically by environmental factors and produce various cytokines, thus playing a role in tissue homeostasis, diseases including allergic diseases, and parasite elimination. ILC2s were first reported as cells abundantly present in fat-associated lymphoid clusters in adipose tissue. However, subsequent studies revealed their presence in various tissues throughout the body, acting as key players in tissue-specific diseases. Recent histologic analyses revealed that ILC2s are concentrated in specific regions in tissues, such as the lamina propria and perivascular regions, with their function being controlled by the surrounding cells, such as epithelial cells and other immune cells, via cytokine and lipid production or by cell–cell interactions through surface molecules. Especially, some stromal cells are identified as the niche cells for ILC2s, both in the steady state and under inflammatory conditions, through the production of IL-33 or extracellular-matrix factors. Additionally, peripheral neurons reportedly co-localize with ILC2s and alter their function directly through neurotransmitters. These findings suggest that the different localizations or different cell–cell interactions might affect the function of ILC2s. Furthermore, generally, ILC2s are thought to be tissue-resident cells; however, they occasionally migrate to other tissues and perform a new role; this supports the importance of the microenvironment for their function. We summarize here the current understanding of how the microenvironment controls ILC2 localization and function with the aim of promoting the development of novel diagnostic and therapeutic methods.

scholarly journals The Microbiotic Highway to Health—New Perspective on Food Structure, Gut Microbiota, and Host Inflammation

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1590 ◽  
Author(s):  
Nina Hansen ◽  
Anette Sams
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Gut Hormones ◽  
Host Immune System ◽  
Inflammatory Conditions ◽  
Food Structure ◽  
New Perspective ◽  
And Function ◽  
The Impact

This review provides evidence that not only the content of nutrients but indeed the structural organization of nutrients is a major determinant of human health. The gut microbiota provides nutrients for the host by digesting food structures otherwise indigestible by human enzymes, thereby simultaneously harvesting energy and delivering nutrients and metabolites for the nutritional and biological benefit of the host. Microbiota-derived nutrients, metabolites, and antigens promote the development and function of the host immune system both directly by activating cells of the adaptive and innate immune system and indirectly by sustaining release of monosaccharides, stimulating intestinal receptors and secreting gut hormones. Multiple indirect microbiota-dependent biological responses contribute to glucose homeostasis, which prevents hyperglycemia-induced inflammatory conditions. The composition and function of the gut microbiota vary between individuals and whereas dietary habits influence the gut microbiota, the gut microbiota influences both the nutritional and biological homeostasis of the host. A healthy gut microbiota requires the presence of beneficial microbiotic species as well as vital food structures to ensure appropriate feeding of the microbiota. This review focuses on the impact of plant-based food structures, the “fiber-encapsulated nutrient formulation”, and on the direct and indirect mechanisms by which the gut microbiota participate in host immune function.

scholarly journals Dietary Indole-3-Carbinol Activates AhR in the Gut, Alters Th17-Microbe Interactions, and Exacerbates Insulitis in NOD Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Heather M. Kahalehili ◽  
Nolan K. Newman ◽  
Jamie M. Pennington ◽  
Siva K. Kolluri ◽  
Nancy I. Kerkvliet ◽  
...  
Keyword(s):  
Small Intestine ◽  
Th17 Cells ◽  
Immune Modulation ◽  
Dietary Intervention ◽  
Nod Mice ◽  
Intestinal Microbiome ◽  
Dietary Recommendations ◽  
Targeted Interventions ◽  
Microbial Dysbiosis ◽  
Microbe Interactions

The diet represents one environmental risk factor controlling the progression of type 1 diabetes (T1D) in genetically susceptible individuals. Consequently, understanding which specific nutritional components promote or prevent the development of disease could be used to make dietary recommendations in prediabetic individuals. In the current study, we hypothesized that the immunoregulatory phytochemcial, indole-3-carbinol (I3C) which is found in cruciferous vegetables, will regulate the progression of T1D in nonobese diabetic (NOD) mice. During digestion, I3C is metabolized into ligands for the aryl hydrocarbon receptor (AhR), a transcription factor that when systemically activated prevents T1D. In NOD mice, an I3C-supplemented diet led to strong AhR activation in the small intestine but minimal systemic AhR activity. In the absence of this systemic response, the dietary intervention led to exacerbated insulitis. Consistent with the compartmentalization of AhR activation, dietary I3C did not alter T helper cell differentiation in the spleen or pancreatic draining lymph nodes. Instead, dietary I3C increased the percentage of CD4+RORγt+Foxp3- (Th17 cells) in the lamina propria, intraepithelial layer, and Peyer’s patches of the small intestine. The immune modulation in the gut was accompanied by alterations to the intestinal microbiome, with changes in bacterial communities observed within one week of I3C supplementation. A transkingdom network was generated to predict host-microbe interactions that were influenced by dietary I3C. Within the phylum Firmicutes, several genera (Intestinimonas, Ruminiclostridium 9, and unclassified Lachnospiraceae) were negatively regulated by I3C. Using AhR knockout mice, we validated that Intestinimonas is negatively regulated by AhR. I3C-mediated microbial dysbiosis was linked to increases in CD25high Th17 cells. Collectively, these data demonstrate that site of AhR activation and subsequent interactions with the host microbiome are important considerations in developing AhR-targeted interventions for T1D.

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