scholarly journals The role of dendritic and В-cells in the development of metainflammation of adipose tissue in obesity

2021 ◽  
Vol 16 (1) ◽  
pp. 60-74
Author(s):  
A.E. Abaturov ◽  
A.А. Nikulina
Keyword(s):  
Dendritic Cells ◽  
Adipose Tissue ◽  
Immune System ◽  
B Cells ◽  
Antigen Presentation ◽  
B Lymphocytes ◽  
Adaptive Immune System ◽  
Fine Tuning ◽  
Peripheral Tissues ◽  
Adaptive Immune

The literature review presents modern data on the spectrum of functional capabilities of the main dendritic cells and B-lymphocytes in the development of metainflammation of adipose tissue in obesity. Dendritic cells functionally link innate and adaptive immunity. The functioning of a subpopulation of professional antigen-presenting lymphocytes — dendritic cells determines the processing, antigen presentation, the canalization of cytodifferentiation of naive T-cells, the activation of B-lymphocytes and specific antibody response. The activation of dendritic cells in adipose tissue is largely due to the interaction of Toll-like receptors 2 and 4 of their cytoplasmic membrane with free fatty acids, the excess of which accompanies the process of obesity. Obesity against the background of experimental dendritic cell depletion in adipose tissue is accompanied by a low level of infiltration by proinflammatory macrophages of both adipose and liver tissue in combination with a higher level of insulin sensitivity of peripheral tissues. The data on the possibility of primary activation of the adaptive immune system in some special clusters of visceral adipose tissue are presented: the lymphoid cluster associated with adipose tissue and milky spots. Activated B-cells perform the function of antigen presentation and antibody formation in the development of the immune response and play an important regulatory role in fine tuning the functioning of the immune system. Thus, the data of most studies indicate that in the development of obesity, dendritic cells, in general, contribute to the development of metainflammation. Obesity leads to accumulation of B-2 cells in adipose tissue, more active production of B-cell-associated pro-inflammatory cytokines, and the generation of IgG, which recruits macrophages into adipose tissue. However, nume­rous questions about the regulation of recruiting, activation of dendritic cells and B-cells in the development of obesity remain unclear. In particular, factors are unknown that recruit tolerogenic dendritic and Breg cells, the mechanisms of regulation of their recruitment to different depots of adipose tissue and the possibility of activa­ting these cells, triggers of the synthesis of protective IgM antibodies. Antigens involved in the activation of the adaptive immune system in the development of obesity also remain unknown.

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals Adipocytes, Innate Immunity and Obesity: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alecia M. Blaszczak ◽  
Anahita Jalilvand ◽  
Willa A. Hsueh
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Cells ◽  
Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

SFRP5 Inhibits Early Stages Of B-Cell Differentiation and Modulates Estrogen-Related Changes In The Immune System

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2422-2422
Author(s):  
Takafumi Yokota ◽  
Kenji Oritani ◽  
Takao Sudo ◽  
Tomohiko Ishibashi ◽  
Yukiko Doi ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Molecular Mechanisms ◽  
Adaptive Immune System ◽  
B Cell Differentiation ◽  
B Lymphopoiesis

Abstract A large body of research has demonstrated that the maternal immune system is elaborately regulated during pregnancy to establish immunological tolerance to the fetus. Although our previous works have revealed that female sex hormones, particularly estrogen, play pivotal roles in suppressing maternal B-lymphopoiesis, the precise molecular mechanisms that mediate their functions are largely unknown. Because T and B lymphocytes function coordinately in the adaptive immune system, the inhibition of B-lymphopoiesis during pregnancy should be involved, at least in part, in “maternal-fetal immune tolerance.” Understanding the molecular mechanisms of tolerance would contribute to the development of new methods to inhibit immune responses after organ transplantation, such as rejection by the host or graft-versus-host diseases. The goal of our present study is to identify the molecular pathways through which estrogen exerts its suppressive effect on B-lymphopoiesis. We performed global analyses of estrogen-inducible genes in bone marrow (BM) stromal cells and identified the secreted frizzled-related protein (sFRP) family. A sFRP1-immunoglobulin G (Ig) fusion protein inhibited early differentiation of B-cells originating from BM-derived hematopoietic stem/progenitor cells (HSPC) in culture (Yokota T. et al. Journal of Immunol, 2008). Conversely, sFRP1 deficiency in vivo caused dysregulation of HSPC homeostasis in BM and aberrant increase of peripheral B lymphocytes (Renström J. et al. Cell Stem Cell, 2009). Therefore, in the present study we generated sFRP1 transgenic chimera (TC) mice that produced high levels of circulating sFRP1 after birth to examine the influence of sFRP1 on adult lymphopoiesis in vivo. Further, we generated sFRP5 TC mice using the same procedure to determine whether there were functional differences or redundancies between sFRP1 and sFRP5. The two are most closely related isoforms among the sFRP family and are known to play redundant roles during embryonic development; however, their physiological function in the immune system is largely unknown. Unexpectedly, while only subtle change was detected in the lymphoid lineage of sFRP1 TC mice, we found that the number of B cells was significantly reduced in the sFRP5 TC mice. The frequency of B cells, which normally account for approximately 50% of peripheral leukocytes of wild-type (WT) mice, was reduced to less than 20% in the sFRP5 TC mice. The suppression was likely specific to the B lineage, because overexpression of sFRP5 did not affect myeloid, T, or NK cells. Compared with WT littermates, the body size of sFRP5 TC mice was slightly, but significantly smaller. Thymocyte counts were not affected. In contrast, the number of splenocytes, particularly those of the B lineage, significantly decreased. In BM of sFRP5 TC mice, early B-cell differentiation was inhibited, resulting in the accumulation of cells whose phenotype corresponds to those of common lymphoid progenitors (CLPs). Gene array analyses of the accumulated CLPs indicated that sFRP5 affects the expression of adaptive immune system-related genes. Further, the sFRP5 overexpression was found to induce the expression of Wnt and Notch-related molecules that regulate the integrity of HSPCs. To determine the physiological involvement of sFRP5 in the inhibition of early B-cell differentiation, we exploited mice lacking sFRP5. It is noteworthy that, although the level of sFRP5 expression was minimal in steady-state BM, it was markedly induced after estrogen treatment. We injected water-soluble β-estradiol into WT or sFRP5-null mice for 4 days and evaluated their lympho-hematopoiesis 12 h after the last injection. While the highly HSPC-enriched Lineage- Sca-1+ c-kitHi Flt3- fraction of WT mice was resistant to the treatment, the same fraction of sFRP5-null mice showed a declining trend. Further, although the CLP fraction was significantly reduced in both strains, CLPs of sFRP5-null mice were more sensitive to estrogen than those of WT. We also performed gene expression analyses of WT and sFRP5-null mice after the estrogen treatment. We found that estrogen induced the expression of Hes1 in HSPCs of WT but not sFRP5-null mice. Thus, we conclude that estrogen-inducible sFRP5 blocks the differentiation of HSPCs in BM to B-lymphocytes in the presence of high levels of estrogen, at least in part by activation of the Notch pathway. Disclosures: No relevant conflicts of interest to declare.

scholarly journals T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

2020 ◽  
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

AbstractBackground: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α-synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective: To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals Persistent SARS-CoV-2 presence is companied with defects in adaptive immune system in non-severe COVID-19 patients

2020 ◽  
Author(s):  
Bing Liu ◽  
Junyan Han ◽  
Xiaohuan Cheng ◽  
Long Yu ◽  
Li Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Immune Cells ◽  
Healthy Subjects ◽  
Laboratory Data ◽  
Adaptive Immune System ◽  
Lymphocyte Subpopulations ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

AbstractBackgroundCOVID-19 has been widely spreading. We aim to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding.Methods37 non-severe patients with persistent SARS-CoV-2 presence transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to PP (persistently positive) group, which was further allocated to PPP group (n=19) and PPN group (n=18), according to their testing results after 7 days (N=negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n=37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison.ResultsCompared with PA patients, PP patients had much improved laboratory findings, including WBCs, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, albumin, AST, CRP, SAA, and IL-6. The absolute numbers of CD3+ T cells, CD4+ T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative.ConclusionPersistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients.SummaryDefects in adaptive immune system, including reduced T cells and B cells, were frequently observed in non-severe COVID-19 patients with persistent SARS-CoV-2 shedding. Assessment of immune system could be clinically relevant for discharge management.

scholarly journals The Leptin Axis and Its Association With the Adaptive Immune System in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura García-Estevez ◽  
Silvia González-Martínez ◽  
Gema Moreno-Bueno
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Leptin Receptor ◽  
Adaptive Immune System ◽  
Tumor Infiltrating Lymphocytes ◽  
Cancer Subtypes ◽  
Adaptive Immune ◽  
Infiltrating Lymphocytes

Adipose tissue secretes various peptides, including leptin. This hormone acts through the leptin receptor (Ob-R), which is expressed ubiquitously on the surface of various cells, including breast cancer cells and immune cells. Increasing evidence points to an interaction between the tumor microenvironment, tumor cells, and the immune system. Leptin plays an important role in breast cancer tumorigenesis and may be implicated in activation of the immune system. While breast cancer cannot be considered an immunogenic cancer, the triple-negative subtype is an exception. Specific immune cells - tumor infiltrating lymphocytes - are involved in the immune response and act as predictive and prognostic factors in certain breast cancer subtypes. The aim of this article is to review the interaction between adipose tissue, through the expression of leptin and its receptor, and the adaptive immune system in breast cancer.

scholarly journals Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease

2021 ◽  
Vol 8 (5) ◽  
pp. e1036
Author(s):  
Zhaoqi Yan ◽  
Wei Yang ◽  
Hairong Wei ◽  
Marissa N. Dean ◽  
David G. Standaert ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Parkinson Disease ◽  
Peripheral Blood ◽  
Cytokine Production ◽  
Early Stage ◽  
Adaptive Immune System ◽  
Th2 Cells ◽  
Adaptive Immune

ObjectiveTo determine the activation status and cytokine profiles of CD4+ T cells, CD8+ T cells, and CD19+ B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs).MethodsPeripheral blood samples from 41 patients with early-stage PD and 40 HCs were evaluated. Peripheral blood mononuclear cells were analyzed by flow cytometry for surface markers and intracellular cytokine production. Correlations of immunologic changes and clinical parameters were analyzed.ResultsAdaptive immunity plays a role in the pathogenesis of PD, yet the contribution of T cells and B cells, especially cytokine production by these cells, is poorly understood. We demonstrate that naive CD4+ and naive CD8+ T cells are significantly decreased in patients with PD, whereas central memory CD4+ T cells are significantly increased in patients with PD. Furthermore, IL-17–producing CD4+ Th17 cells, IL-4–producing CD4+ Th2 cells, and IFN-γ–producing CD8+ T cells are significantly increased in patients with PD. Regarding B cells, we observed a decrease in naive B cells and an increase in nonswitched memory and double-negative B cells. As well, TNF-α–producing CD19+ B cells were significantly increased in patients with PD. Notably, some of the changes observed in CD4+ T cells and B cells were associated with clinical motor disease severity.ConclusionsThese findings suggest that alterations in the adaptive immune system may promote clinical disease in PD by skewing to a more proinflammatory state in the early-stage PD patient cohort. Our study may shed light on potential immunotherapies targeting dysregulated CD4+ T cells, CD8+ T cells, and CD19+ B cells in patients with PD.

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