scholarly journals Maternal vitamin D deficiency increases the risk of obesity in male mice offspring by affecting the immune response

2020 ◽  
Author(s):  
Pei Li ◽  
Ping Li ◽  
Yuanlin Liu ◽  
Weijiang Liu ◽  
Lanlan Zha ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Immune Cell ◽  
Male Offspring ◽  
Inflammatory Factors ◽  
Cell Populations ◽  
Male Mice ◽  
Gene Expressions ◽  
M1 Macrophage ◽  
Obese Male

AbstractRecently, many epidemiological and animal studies have indicated that obesity have their origin in the early stages of life including the inappropriate balance of some nutrients, the objective of this study is to determine the risk of obesity in male mice offspring as a consequence of maternal VD deficiency-mediated disordering of the immune response. Four-week-old C57BL/6J female mice were fed VD-deficient or normal reproductive diets during pregnancy and lactation. Their male offspring were weighted and euthanized after being fed control and high-fat diets (HFD) for 16 weeks starting at the weaning. The serum was collected for biochemical analyses. Epididymal (eWAT) and inguinal (iWAT) white adipose tissues were excised for histological examination, immunohistochemistry, gene expressions of inflammatory factors, and for determining the proportions of immune cells by flow cytometry. Insufficient maternal VD intake exacerbated the development of obesity both in non-obese and obese male offspring as evidenced by larger adipose cells and abnormal glucose and lipid metabolisms. Also, the expression of proinflammatory cytokine genes was increased and that of anti-inflammatory cytokines was decreased in maternal VD-deficient groups in the eWAT and/or iWAT. This was accompanied by higher levels of TNF-α or/and INF-β, and lower levels of IL-4 and IL-10. Insufficient maternal VD intake was also observed to induce a shift in the profiles of immune cells in the eWAT and/or iWAT, resulting in increased percentages of M1 macrophage, ATDCs, and CD4+ and CD8+ T cells, but caused a significant decrease in the percentage of M2 macrophages, both in non-obese and obese male offspring. All these changes in the immune cell profile were more obvious in the eWAT than in the iWAT. These results indicated that insufficient maternal VD intake promoted the development of obesity in male offspring by modulating the immune cell populations and causing a polarization in the adipose depots.ImportanceEvidence in this study has indicated that insufficient maternal VD intake promotes the development of obesity in the male offspring by modulating the recruitment of immune cell populations and their polarization as well as the expression and secretion of proinflammatory adipokines in the adipose depots in a weight-independent manner, which is more obvious in eWAT than that in the iWAT.

scholarly journals TrackSOM: mapping immune response dynamics through sequential clustering of time- and disease-course single-cell cytometry data

2021 ◽  
Author(s):  
Givanna Haryono Putri ◽  
Jonathan Chung ◽  
Davis N Edwards ◽  
Felix Marsh-Wakefield ◽  
Suat Dervish ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
West Nile Virus ◽  
Immune Cells ◽  
Immune Cell ◽  
West Nile Virus Infection ◽  
Cell Populations ◽  
Disease Course ◽  
Response Dynamics ◽  
Over Time

Mapping the dynamics of immune cell populations over time or disease-course is key to understanding immunopathogenesis and devising putative interventions. We present TrackSOM, an algorithm which delineates cellular populations and tracks their development over a time- or disease-course of cytometry datasets. We demonstrate TrackSOM-enabled elucidation of the immune response to West Nile Virus infection in mice, uncovering heterogeneous sub-populations of immune cells and relating their functional evolution to disease severity. TrackSOM is easy to use, encompasses few parameters, is quick to execute, and enables an integrative and dynamic overview of the immune system kinetics that underlie disease progression and/or resolution.

scholarly journals The immune response and aging in chronic inflammatory demyelinating polyradiculoneuropathy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kathleen M. Hagen ◽  
Shalina S. Ousman
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Older Patients ◽  
Potential Role ◽  
Immune Cell ◽  
Chronic Inflammatory Demyelinating Polyradiculoneuropathy ◽  
Cell Populations ◽  
Relapsing Remitting ◽  
Progressive Course

AbstractChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consists of various autoimmune subtypes in which the peripheral nervous system (PNS) is attacked. CIDP can follow a relapsing-remitting or progressive course where the resultant demyelination caused by immune cells (e.g., T cells, macrophages) and antibodies can lead to disability in patients. Importantly, the age of CIDP patients has a role in their symptomology and specific variants have been associated with differing ages of onset. Furthermore, older patients have a decreased frequency of functional recovery after CIDP insult. This may be related to perturbations in immune cell populations that could exacerbate the disease with increasing age. In the present review, the immune profile of typical CIDP will be discussed followed by inferences into the potential role of relevant aging immune cell populations. Atypical variants will also be briefly reviewed followed by an examination of the available studies on the immunology underlying them.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Quantitative Methodologies to Dissect Immune Cell Mechanobiology

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 851
Author(s):  
Veronika Pfannenstill ◽  
Aurélien Barbotin ◽  
Huw Colin-York ◽  
Marco Fritzsche
Keyword(s):  
Mechanical Properties ◽  
Immune Response ◽  
Time Scales ◽  
Immune Cells ◽  
Cell Mechanics ◽  
Immune Cell ◽  
Biological Significance ◽  
Force Generation ◽  
Tissue Microenvironment ◽  
And Behavior

Mechanobiology seeks to understand how cells integrate their biomechanics into their function and behavior. Unravelling the mechanisms underlying these mechanobiological processes is particularly important for immune cells in the context of the dynamic and complex tissue microenvironment. However, it remains largely unknown how cellular mechanical force generation and mechanical properties are regulated and integrated by immune cells, primarily due to a profound lack of technologies with sufficient sensitivity to quantify immune cell mechanics. In this review, we discuss the biological significance of mechanics for immune cells across length and time scales, and highlight several experimental methodologies for quantifying the mechanics of immune cells. Finally, we discuss the importance of quantifying the appropriate mechanical readout to accelerate insights into the mechanobiology of the immune response.

scholarly journals Molecular and Clinical Characterization of LAG3 in Breast Cancer Through 2994 Samples

2020 ◽  
Author(s):  
Qiang Liu ◽  
Yihang Qi ◽  
Jie Zhai ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Immune Cell ◽  
Immune Checkpoints ◽  
Cell Populations ◽  
Potential Biomarker ◽  
The Impact

Abstract Background Despite the promising impact of cancer immunotherapy targeting CTLA4 and PD1/PDL1, a large number of cancer patients fail to respond. LAG3 (Lymphocyte Activating 3), also named CD233, is a protein Coding gene served as alternative inhibitory receptors to be targeted in the clinic. The impact of LAG3 on immune cell populations and co-regulation of immune response in breast cancer remained largely unknown. Methods To characterize the role of LAG3 in breast cancer, we investigated transcriptome data and associated clinical information derived from a total of 2994 breast cancer patients. Results We observed that LAG3 was closely correlated with major molecular and clinical characteristics, and was more likely to be enriched in higher malignant subtype, suggesting LAG3 was a potential biomarker of triple-negative breast cancer. Furthermore, we estimated the landscape of relationship between LAG3 and ten types of cell populations in breast cancer. Gene ontology analysis revealed LAG3 were strongly correlated with immune response and inflammatory activities. We investigated the correlation pattern between LAG3 and immune modulators in pan-cancer, especially the synergistic role of LAG3 with other immune checkpoints members in breast cancer. Conclusions LAG3 expression was closely related to malignancy of breast cancer and might serve as a potential biomarker; LAG3 might plays an important role in regulating tumor immune microenvironment, not only T cells, but also other immune cells. More importantly, LAG3 might synergize with CTLA4, PD1/ PDL1 and other immune checkpoints, thereby lending more evidences to combination cancer immunotherapy by targeting LAG3, PD1/PDL1, and CTLA4 together.

scholarly journals Identification of immune-based prostate cancer subtypes using mRNA expression

2020 ◽  
Author(s):  
Jukun Song ◽  
Song He ◽  
Wei Wang ◽  
Jiaming Su ◽  
Dongbo Yuan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Immune Cells ◽  
Immune Cell ◽  
Molecular Classification ◽  
Cell Types ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Cell Subpopulation ◽  
Immune Cell Infiltration

Abstract Background Immune infiltration of Prostate cancer (PCa) was highly related to clinical outcomes. However, previous works failed to elucidate the diversity of different immune cell types that make up the function of the immune response system. The aim of the study was to uncover the composition of TIICs in PCa utilizing the CIBERSORT algorithm and further reveal the molecular characteristics of PCa subtypes. Method In the present work, we employed the CIBERSORT method to evaluate the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We analyzed the correlation between immune cell infiltration and clinical information. The tumor-infiltrating immune cells of the TCGA PCa cohort were analyzed for the first time. The fractions of 22 immune cell types were imputed to determine the correlation between each immune cell subpopulation and clinical feature. Three types of molecular classification were identified via R-package of “CancerSubtypes”. The functional enrichment was analyzed in each subtype. The submap and TIDE algorithm were used to predict the clinical response to immune checkpoint blockade, and GDSC was employed to screen chemotherapeutic targets for the potential treatment of PCa. Results In current work, we utilized the CIBERSORT algorithm to assess the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We investigated the correlation between immune cell infiltration and clinical data. The tumor-infiltrating immune cells in the TCGA PCa cohort were analyzed. The 22 immune cells were also calculated to determine the correlation between each immune cell subpopulation and survival and response to chemotherapy. Three types of molecular classification were identified. Each subtype has specific molecular and clinical characteristics. Meanwhile, Cluster I is defined as advanced PCa, and is more likely to respond to immunotherapy. Conclusions Our results demonstrated that differences in immune response may be important drivers of PCa progression and response to treatment. The deconvolution algorithm of gene expression microarray data by CIBERSOFT provides useful information about the immune cell composition of PCa patients. In addition, we have found a subtype of immunopositive PCa subtype and will help to explore the reasons for the poor effect of PCa on immunotherapy, and it is expected that immunotherapy will be used to guide the individualized management and treatment of PCa patients.

scholarly journals The Hippo Pathway: Immunity and Cancer

Cancers ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 94 ◽  
Author(s):  
Zaid Taha ◽  
Helena Janse van Rensburg ◽  
Xiaolong Yang
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mammalian Cells ◽  
Immune Cell ◽  
Hippo Pathway ◽  
Tissue Homeostasis ◽  
Hippo Signaling ◽  
Core Components ◽  
The Hippo Pathway ◽  
Future Work

Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

scholarly journals Fluoropyrimidine Modulation of the Anti-Tumor Immune Response―Prospects for Improved Colorectal Cancer Treatment

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1641
Author(s):  
William H. Gmeiner
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Adjuvant Chemotherapy ◽  
Tumor Immunity ◽  
Immune Checkpoint ◽  
Survival Benefit ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Cell Populations ◽  
Colorectal Cancer Treatment

Chemotherapy modulates the anti-tumor immune response and outcomes depend on the balance of favorable and unfavorable effects of drugs on anti-tumor immunity. 5-Florouracil (5-FU) is widely used in adjuvant chemotherapy regimens to treat colorectal cancer (CRC) and provides a survival benefit. However, survival remains poor for CRC patients with advanced and metastatic disease and immune checkpoint blockade therapy benefits only a sub-set of CRC patients. Here we discuss the effects of 5-FU-based chemotherapy regimens to the anti-tumor immune response. We consider how different aspects of 5-FU’s multi-factorial mechanism differentially affect malignant and immune cell populations. We summarize recent studies with polymeric fluoropyrimidines (e.g., F10, CF10) that enhance DNA-directed effects and discuss how such approaches may be used to enhance the anti-tumor immune response and improve outcomes.

scholarly journals Antibiotic Therapy Does Not Alter the Humoral Response to Vaccination for Porcine Circovirus 2 in Weaned Pigs

2019 ◽  
Vol 6 (2) ◽  
pp. 51
Author(s):  
Jonathan E. Fogle ◽  
Jenna A. Scott ◽  
Glen W. Almond
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Antibiotic Therapy ◽  
Humoral Immunity ◽  
Immune Cell ◽  
Humoral Response ◽  
Porcine Circovirus ◽  
Cell Populations ◽  
Antibiotic Administration ◽  
Weaned Pigs

Recent reports suggest that antibiotic therapy may either reduce or enhance the immune response to various porcine vaccines. Based upon these findings, we asked if antibiotic therapy alters immune cell populations, as measured by flow cytometry and/or vaccine-specific humoral immunity, as measured by sample to positive (S/P) antibody ratios. Here, we investigated the immuno-modulatory effects of enrofloxacin, ceftiofur, and tulathromycin on the immune response to a Mycoplasma hyopneumoniae (M. hyopneumoniae) and porcine circovirus type 2 (PCV-2) combination vaccine in weaned pigs. Maternal antibody likely interfered with the induction of immunity to M. hyopneumoniae. Antibiotic administration did not affect immune cell populations, as assessed by flow cytometry and did not affect the induction of humoral immunity to PCV-2.

scholarly journals Impact of systemic therapy on circulating leukocyte populations in patients with metastatic breast cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna-Maria Larsson ◽  
Anna Roxå ◽  
Karin Leandersson ◽  
Caroline Bergenfelz
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Natural Killer ◽  
Endocrine Therapy ◽  
Immune Cells ◽  
Systemic Therapy ◽  
Immune Cell ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Cell Populations

Abstract Tumors affect the immune system, locally and systemically. The frequencies of specific circulating immune cell populations correlate with disease progression as well as prognosis of the patients. Although largely neglected, conventional antitumoral therapies often possess immunomodulatory properties and affect the levels of specific immune cell populations. Most information, however, derive from animal or in vitro studies. As this could impact prognosis as well as response to therapy, further studies of the effects of treatment on circulating immune cells in patients are warranted. In this pilot study, we evaluated a wide panel of circulating immune cells over time (up to six months) in ten patients with metastatic breast cancer receiving standard antitumoral regimens. Overall, endocrine therapy tends to enrich for natural killer (NK) and natural killer T (NKT) cells in the circulation, whereas both chemotherapy and endocrine therapy reduce the levels of circulating monocytic myeloid-derived suppressor cells (Mo-MDSCs). This indicates that the systemic immunosuppressive profile observed in patients tends to revert over the course of systemic therapy and holds promise for future combination treatment with standard antitumoral agents and immunotherapy.

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