Long Noncoding RNA in Myeloid and Lymphoid Cell Differentiation, Polarization and Function

Long noncoding RNA (lncRNA) are a class of endogenous, non-protein coding RNAs that are increasingly being associated with various cellular functions and diseases. Yet, despite their ubiquity and abundance, only a minute fraction of these molecules has an assigned function. LncRNAs show tissue-, cell-, and developmental stage-specific expression, and are differentially expressed under physiological or pathological conditions. The role of lncRNAs in the lineage commitment of immune cells and shaping immune responses is becoming evident. Myeloid cells and lymphoid cells are two major classes of immune systems that work in concert to initiate and amplify innate and adaptive immunity in vertebrates. In this review, we provide mechanistic roles of lncRNA through which these noncoding RNAs can directly participate in the differentiation, polarization, and activation of myeloid (monocyte, macrophage, and dendritic cells) and lymphoid cells (T cells, B cells, and NK cells). While our knowledge on the role of lncRNA in immune cell differentiation and function has improved in the past decade, further studies are required to unravel the biological role of lncRNAs and identify novel mechanisms of lncRNA functions in immune cells. Harnessing the regulatory potential of lncRNAs can provide novel diagnostic and therapeutic targets in treating immune cell related diseases.

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LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation

Nature Communications ◽

10.1038/s41467-018-08153-2 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 12

Author(s):

Valentina Profumo ◽

Barbara Forte ◽

Stefano Percio ◽

Federica Rotundo ◽

Valentina Doldi ◽

...

Keyword(s):

Cell Differentiation ◽

Basal Cell ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Host Gene ◽

Leader Role

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Role of Macrophages and Microglia in Zebrafish Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms21134768 ◽

2020 ◽

Vol 21 (13) ◽

pp. 4768 ◽

Cited By ~ 4

Author(s):

Susanna R. Var ◽

Christine A. Byrd-Jacobs

Keyword(s):

Nervous System ◽

Immune Cells ◽

Immune Cell ◽

Innate Immune ◽

Inflammatory Processes ◽

The Central Nervous System ◽

And Function ◽

High Degree ◽

Human Nerve

Currently, there is no treatment for recovery of human nerve function after damage to the central nervous system (CNS), and there are limited regenerative capabilities in the peripheral nervous system. Since fish are known for their regenerative abilities, understanding how these species modulate inflammatory processes following injury has potential translational importance for recovery from damage and disease. Many diseases and injuries involve the activation of innate immune cells to clear damaged cells. The resident immune cells of the CNS are microglia, the primary cells that respond to infection and injury, and their peripheral counterparts, macrophages. These cells serve as key modulators of development and plasticity and have been shown to be important in the repair and regeneration of structure and function after injury. Zebrafish are an emerging model for studying macrophages in regeneration after injury and microglia in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. These fish possess a high degree of neuroanatomical, neurochemical, and emotional/social behavioral resemblance with humans, serving as an ideal simulator for many pathologies. This review explores literature on macrophage and microglial involvement in facilitating regeneration. Understanding innate immune cell behavior following damage may help to develop novel methods for treating toxic and chronic inflammatory processes that are seen in trauma and disease.

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Dietary and Physiological Effects of Zinc on the Immune System

Annual Review of Nutrition ◽

10.1146/annurev-nutr-122019-120635 ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Inga Wessels ◽

Henrike Josephine Fischer ◽

Lothar Rink

Keyword(s):

Immune Responses ◽

Immune Cells ◽

Immune Cell ◽

Current Knowledge ◽

Annual Review ◽

Publication Date ◽

Biological Processes ◽

And Function ◽

Broad Overview

Evidence for the importance of zinc for all immune cells and for mounting an efficient and balanced immune response to various environmental stressors has been accumulating in recent years. This article describes the role of zinc in fundamental biological processes and summarizes our current knowledge of zinc's effect on hematopoiesis, including differentiation into immune cell subtypes. In addition, the important role of zinc during activation and function of immune cells is detailed and associated with the specific immune responses to bacteria, parasites, and viruses. The association of zinc with autoimmune reactions and cancers as diseases with increased or decreased immune responses is also discussed. This article provides a broad overview of the manifold roles that zinc, or its deficiency, plays in physiology and during various diseases. Consequently, we discuss why zinc supplementation should be considered, especially for people at risk of deficiency. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Physiological role of urothelial cancer-associated one long noncoding RNA in human skeletogenic cell differentiation

Journal of Cellular Physiology ◽

10.1002/jcp.26285 ◽

2018 ◽

Vol 233 (6) ◽

pp. 4825-4840 ◽

Cited By ~ 8

Author(s):

Takanori Ishikawa ◽

Takashi Nishida ◽

Mitsuaki Ono ◽

Takeshi Takarada ◽

Ha Thi Nguyen ◽

...

Keyword(s):

Cell Differentiation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Urothelial Cancer ◽

Physiological Role

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Biology and pathology of the uterine microenvironment and its natural killer cells

Cellular and Molecular Immunology ◽

10.1038/s41423-021-00739-z ◽

2021 ◽

Author(s):

Fuyan Wang ◽

Anita Ellen Qualls ◽

Laia Marques-Fernandez ◽

Francesco Colucci

Keyword(s):

Natural Killer ◽

Fetal Growth ◽

Immune Cells ◽

Smooth Muscle Actin ◽

Lymphoid Cells ◽

Unk Cells ◽

New Frontier ◽

Uterine Mucosa ◽

Blastocyst Implantation ◽

And Function

AbstractTissues are the new frontier of discoveries in immunology. Cells of the immune system are an integral part of tissue physiology and immunity. Determining how immune cells inhabit, housekeep, and defend gut, lung, brain, liver, uterus, and other organs helps revealing the intimate details of tissue physiology and may offer new therapeutic targets to treat pathologies. The uterine microenvironment modulates the development and function of innate lymphoid cells [ILC, largely represented by natural killer (NK) cells], macrophages, T cells, and dendritic cells. These immune cells, in turn, contribute to tissue homeostasis. Regulated by ovarian hormones, the human uterine mucosa (endometrium) undergoes ~400 monthly cycles of breakdown and regeneration from menarche to menopause, with its fibroblasts, glands, blood vessels, and immune cells remodeling the tissue into the transient decidua. Even more transformative changes occur upon blastocyst implantation. Before the placenta is formed, the endometrial glands feed the embryo by histiotrophic nutrition while the uterine spiral arteries are stripped of their endothelial layer and smooth muscle actin. This arterial remodeling is carried out by invading fetal trophoblast and maternal immune cells, chiefly uterine NK (uNK) cells, which also assist fetal growth. The transformed arteries no longer respond to maternal stimuli and meet the increasing demands of the growing fetus. This review focuses on how the everchanging uterine microenvironment affects uNK cells and how uNK cells regulate homeostasis of the decidua, placenta development, and fetal growth. Determining these pathways will help understand the causes of major pregnancy complications.

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How Changes in the Nutritional Landscape Shape Gut Immunometabolism

Nutrients ◽

10.3390/nu13030823 ◽

2021 ◽

Vol 13 (3) ◽

pp. 823

Author(s):

Jian Tan ◽

Duan Ni ◽

Rosilene V. Ribeiro ◽

Gabriela V. Pinget ◽

Laurence Macia

Keyword(s):

Immune Cells ◽

Metabolic Pathways ◽

Immune Cell ◽

Food Additives ◽

Cell Activity ◽

Inflammatory Cells ◽

Therapeutic Approaches ◽

Food Antigens ◽

And Function ◽

Micro Organisms

Cell survival, proliferation and function are energy-demanding processes, fuelled by different metabolic pathways. Immune cells like any other cells will adapt their energy production to their function with specific metabolic pathways characteristic of resting, inflammatory or anti-inflammatory cells. This concept of immunometabolism is revolutionising the field of immunology, opening the gates for novel therapeutic approaches aimed at altering immune responses through immune metabolic manipulations. The first part of this review will give an extensive overview on the metabolic pathways used by immune cells. Diet is a major source of energy, providing substrates to fuel these different metabolic pathways. Protein, lipid and carbohydrate composition as well as food additives can thus shape the immune response particularly in the gut, the first immune point of contact with food antigens and gastrointestinal tract pathogens. How diet composition might affect gut immunometabolism and its impact on diseases will also be discussed. Finally, the food ingested by the host is also a source of energy for the micro-organisms inhabiting the gut lumen particularly in the colon. The by-products released through the processing of specific nutrients by gut bacteria also influence immune cell activity and differentiation. How bacterial metabolites influence gut immunometabolism will be covered in the third part of this review. This notion of immunometabolism and immune function is recent and a deeper understanding of how lifestyle might influence gut immunometabolism is key to prevent or treat diseases.

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Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02149-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zimo Zhou ◽

Mohammad Showkat Hossain ◽

Da Liu

Keyword(s):

Bone Regeneration ◽

Osteogenic Differentiation ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Osteoblast Differentiation ◽

Osteoclast Differentiation ◽

Complex Processes ◽

Osteogenic Induction ◽

Novel Target

AbstractOsteogenic differentiation and bone regeneration are complex processes involving multiple genes and multiple steps. In this review, we summarize the effects of the long noncoding RNA (lncRNA) H19 on osteogenic differentiation.Osteogenic differentiation includes matrix secretion and calcium mineralization as hallmarks of osteoblast differentiation and the absorption of calcium and phosphorus as hallmarks of osteoclast differentiation. Mesenchymal stem cells (MSCs) form osteoprogenitor cells, pre-osteoblasts, mature osteoblasts, and osteocytes through induction and differentiation. lncRNAs regulate the expression of coding genes and play essential roles in osteogenic differentiation and bone regeneration. The lncRNA H19 is known to have vital roles in osteogenic induction.This review highlights the role of H19 as a novel target for osteogenic differentiation and the promotion of bone regeneration.

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When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

International Journal of Cell Biology ◽

10.1155/2011/470597 ◽

2011 ◽

Vol 2011 ◽

pp. 1-13 ◽

Cited By ~ 16

Author(s):

Katrin Schlie ◽

Jaeline E. Spowart ◽

Luke R. K. Hughson ◽

Katelin N. Townsend ◽

Julian J. Lum

Keyword(s):

Tumor Microenvironment ◽

Cancer Cells ◽

Immune Cells ◽

Immune Cell ◽

Treatment Strategies ◽

Patient Treatment ◽

Low Oxygen ◽

Tumor Environment ◽

And Function ◽

The Impact

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism. Autophagy upregulation in cancer cells liberates nutrients, decreases the buildup of reactive oxygen species, and aids in the clearance of misfolded proteins. Together, these features impart a survival advantage for cancer cells in the tumor microenvironment. This observation has led to intense research efforts focused on developing autophagy-modulating drugs for cancer patient treatment. However, other cells that infiltrate the tumor environment such as immune cells also encounter hypoxia likely resulting in hypoxia-induced autophagy. In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system.

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Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens

Gut ◽

10.1136/gutjnl-2016-313214 ◽

2017 ◽

Vol 67 (5) ◽

pp. 847-859 ◽

Cited By ~ 11

Author(s):

Allison Cabinian ◽

Daniel Sinsimer ◽

May Tang ◽

Youngsoon Jang ◽

Bongkum Choi ◽

...

Keyword(s):

Gut Microbiota ◽

Immune Cells ◽

Immune Cell ◽

Lymphocyte Activation ◽

Premature Death ◽

Enteric Pathogens ◽

Immune Protection ◽

Intestinal Immunity ◽

Cell Responses ◽

And Function

BackgroundInteractions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field.AimWe have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is.MethodsExpression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium.ResultsSLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC)TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death.ConclusionsSLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.

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